Biomolecular engineering
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Biomolecular engineering is the application of engineering principles and practices to the purposeful manipulation of molecules of biological origin. Biomolecular engineers integrate knowledge of
biological processes Biological processes are those processes that are vital for an organism to live, and that shape its capacities for interacting with its environment. Biological processes are made of many chemical reactions or other events that are involved in the ...
with the core knowledge of
chemical engineering Chemical engineering is an engineering field which deals with the study of operation and design of chemical plants as well as methods of improving production. Chemical engineers develop economical commercial processes to convert raw materials in ...
in order to focus on molecular level solutions to issues and problems in the life sciences related to the
environment Environment most often refers to: __NOTOC__ * Natural environment, all living and non-living things occurring naturally * Biophysical environment, the physical and biological factors along with their chemical interactions that affect an organism or ...
,
agriculture Agriculture or farming is the practice of cultivating plants and livestock. Agriculture was the key development in the rise of sedentary human civilization, whereby farming of domesticated species created food surpluses that enabled people ...
,
energy In physics, energy (from Ancient Greek: ἐνέργεια, ''enérgeia'', “activity”) is the quantitative property that is transferred to a body or to a physical system, recognizable in the performance of work and in the form of ...
, industry,
food production The food industry is a complex, global network of diverse businesses that supplies most of the food consumed by the world's population. The food industry today has become highly diversified, with manufacturing ranging from small, traditional, ...
,
biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used ...
and medicine. Biomolecular engineers purposefully manipulate
carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may o ...
s,
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s,
nucleic acid Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main ...
s and
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids in ...
s within the framework of the relation between their structure (see:
nucleic acid structure Nucleic acid structure refers to the structure of nucleic acids such as DNA and RNA. Chemically speaking, DNA and RNA are very similar. Nucleic acid structure is often divided into four different levels: primary, secondary, tertiary, and quater ...
,
carbohydrate chemistry Carbohydrate chemistry is a subdiscipline of chemistry primarily concerned with the detection, synthesis, structure, and function of carbohydrates. Due to the general structure of carbohydrates, their synthesis is often preoccupied with the sele ...
,
protein structure Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, the monomers of the polymer. A single amino acid monom ...
,), function (see:
protein function Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respond ...
) and properties and in relation to applicability to such areas as
environmental remediation Environmental remediation deals with the removal of pollution or contaminants from environmental media such as soil, groundwater, sediment, or surface water. Remedial action is generally subject to an array of regulatory requirements, and may al ...
, crop and livestock production, biofuel cells and biomolecular diagnostics. The thermodynamics and kinetics of molecular recognition in
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s,
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
, DNA hybridization, bio-conjugation/bio-immobilization and bioseparations are studied. Attention is also given to the rudiments of engineered biomolecules in
cell signaling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
, cell growth kinetics, biochemical pathway engineering and bioreactor engineering.


Timeline


History

During World War II, the need for large quantities of
penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from '' Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum usin ...
of acceptable quality brought together chemical engineers and microbiologists to focus on penicillin production. This created the right conditions to start a chain of reactions that lead to the creation of the field of biomolecular engineering. Biomolecular engineering was first defined in 1992 by the
U.S. National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late 1 ...
as research at the interface of chemical engineering and biology with an emphasis at the molecular level". Although first defined as research, biomolecular engineering has since become an academic discipline and a field of engineering practice. Herceptin, a humanized Mab for breast cancer treatment, became the first drug designed by a biomolecular engineering approach and was approved by the U.S. FDA. Also, ''Biomolecular Engineering'' was a former name of the journal ''
New Biotechnology ''New Biotechnology'' is a peer-reviewed scientific journal and the official journal of the European Federation of Biotechnology. It is published bimonthly by Elsevier. The journal covers research, industrial, and commercial aspects of biotechnolog ...
''.


Future

Bio-inspired technologies of the future can help explain biomolecular engineering. Looking at the
Moore's law Moore's law is the observation that the number of transistors in a dense integrated circuit (IC) doubles about every two years. Moore's law is an observation and projection of a historical trend. Rather than a law of physics, it is an empi ...
"Prediction", in the future
quantum In physics, a quantum (plural quanta) is the minimum amount of any physical entity ( physical property) involved in an interaction. The fundamental notion that a physical property can be "quantized" is referred to as "the hypothesis of quantizat ...
and biology-based processors are "big" technologies. With the use of biomolecular engineering, the way our processors work can be manipulated in order to function in the same sense a biological cell work. Biomolecular engineering has the potential to become one of the most important scientific disciplines because of its advancements in the analyses of gene expression patterns as well as the purposeful manipulation of many important biomolecules to improve functionality. Research in this field may lead to new drug discoveries, improved therapies, and advancement in new bioprocess technology. With the increasing knowledge of biomolecules, the rate of finding new high-value molecules including but not limited to
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
,
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s,
vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.
s, and therapeutic
peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...
s will continue to accelerate. Biomolecular engineering will produce new designs for therapeutic drugs and high-value biomolecules for treatment or prevention of cancers, genetic diseases, and other types of
metabolic diseases Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances ( substra ...
. Also, there is anticipation of
industrial enzymes Industrial enzymes are enzymes that are commercially used in a variety of industries such as pharmaceuticals, chemical production, biofuels, food & beverage, and consumer products. Due to advancements in recent years, biocatalysis through isolated ...
that are engineered to have desirable properties for process improvement as well the manufacturing of high-value biomolecular products at a much lower production cost. Using
recombinant technology Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fou ...
, new antibiotics that are active against resistant strains will also be produced.


Basic biomolecules

Biomolecular engineering deals with the manipulation of many key biomolecules. These include, but are not limited to, proteins, carbohydrates, nucleic acids, and lipids. These molecules are the basic building blocks of life and by controlling, creating, and manipulating their form and function there are many new avenues and advantages available to society. Since every
biomolecule A biomolecule or biological molecule is a loosely used term for molecules present in organisms that are essential to one or more typically biological processes, such as cell division, morphogenesis, or developmental biology, development. Biom ...
is different, there are a number of techniques used to manipulate each one respectively.


Proteins

Proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
are polymers that are made up of
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
chains linked with peptide bonds. They have four distinct levels of structure: primary, secondary, tertiary, and quaternary. Primary structure refers to the amino acid backbone sequence. Secondary structure focuses on minor conformations that develop as a result of the hydrogen bonding between the amino acid chain. If most of the protein contains intermolecular hydrogen bonds it is said to be fibrillar, and the majority of its secondary structure will be beta sheets. However, if the majority of the orientation contains intramolecular hydrogen bonds, then the protein is referred to as globular and mostly consists of
alpha helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ear ...
. There are also conformations that consist of a mix of alpha helices and beta sheets as well as a
beta helix A beta helix is a tandem protein repeat structure formed by the association of parallel beta strands in a helical pattern with either two or three faces. The beta helix is a type of solenoid protein domain. The structure is stabilized by inter- ...
es with an alpha sheets. The tertiary structure of proteins deal with their folding process and how the overall molecule is arranged. Finally, a quaternary structure is a group of tertiary proteins coming together and binding. With all of these levels, proteins have a wide variety of places in which they can be manipulated and adjusted. Techniques are used to affect the amino acid sequence of the protein (site-directed mutagenesis), the folding and conformation of the protein, or the folding of a single tertiary protein within a quaternary protein matrix. Proteins that are the main focus of manipulation are typically
enzymes Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...
. These are proteins that act as
catalysts Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
for
biochemical reaction Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
s. By manipulating these catalysts, the reaction rates, products, and effects can be controlled. Enzymes and proteins are important to the biological field and research that there are specific divisions of engineering focusing only on proteins and enzymes.


Carbohydrates

Carbohydrates In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or m ...
are another important biomolecule. These are polymers, called
polysaccharides Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with w ...
, which are made up of chains of simple sugars connected via
glycosidic bonds A glycosidic bond or glycosidic linkage is a type of covalent bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate. A glycosidic bond is formed between the hemiacetal or hemiketal gr ...
. These
monosaccharides Monosaccharides (from Greek '' monos'': single, '' sacchar'': sugar), also called simple sugars, are the simplest forms of sugar and the most basic units ( monomers) from which all carbohydrates are built. They are usually colorless, water ...
consist of a five to six carbon ring that contains carbon, hydrogen, and oxygen - typically in a 1:2:1 ratio, respectively. Common monosaccharides are
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
,
fructose Fructose, or fruit sugar, is a ketonic simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorb ...
, and ribose. When linked together monosaccharides can form
disaccharides A disaccharide (also called a double sugar or ''biose'') is the sugar formed when two monosaccharides are joined by glycosidic linkage. Like monosaccharides, disaccharides are simple sugars soluble in water. Three common examples are sucrose, lac ...
,
oligosaccharides An oligosaccharide (/ˌɑlɪgoʊˈsækəˌɹaɪd/; from the Greek ὀλίγος ''olígos'', "a few", and σάκχαρ ''sácchar'', "sugar") is a saccharide polymer containing a small number (typically two to ten) of monosaccharides (simple suga ...
, and polysaccharides: the nomenclature is dependent on the number of monosaccharides linked together. Common dissacharides, two monosaccharides joined, are
sucrose Sucrose, a disaccharide, is a sugar composed of glucose and fructose subunits. It is produced naturally in plants and is the main constituent of white sugar. It has the molecular formula . For human consumption, sucrose is extracted and refine ...
,
maltose } Maltose ( or ), also known as maltobiose or malt sugar, is a disaccharide formed from two units of glucose joined with an α(1→4) bond. In the isomer isomaltose, the two glucose molecules are joined with an α(1→6) bond. Maltose is the tw ...
, and
lactose Lactose is a disaccharide sugar synthesized by galactose and glucose subunits and has the molecular formula C12H22O11. Lactose makes up around 2–8% of milk (by mass). The name comes from ' (gen. '), the Latin word for milk, plus the suffix ' ...
. Important polysaccharides, links of many monosaccharides, are
cellulose Cellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to many thousands of β(1→4) linked D-glucose units. Cellulose is an important structural component of the primary cell wa ...
,
starch Starch or amylum is a polymeric carbohydrate consisting of numerous glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants for energy storage. Worldwide, it is the most common carbohydrate in human die ...
, and
chitin Chitin ( C8 H13 O5 N)n ( ) is a long-chain polymer of ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is probably the second most abundant polysaccharide in nature (behind only cellulose); an estimated 1 billion tons of chit ...
.
Cellulose Cellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to many thousands of β(1→4) linked D-glucose units. Cellulose is an important structural component of the primary cell wa ...
is a polysaccharide made up of beta 1-4 linkages between repeat glucose monomers. It is the most abundant source of sugar in nature and is a major part of the paper industry.
Starch Starch or amylum is a polymeric carbohydrate consisting of numerous glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants for energy storage. Worldwide, it is the most common carbohydrate in human die ...
is also a polysaccharide made up of glucose monomers; however, they are connected via an alpha 1-4 linkage instead of beta. Starches, particularly
amylase An amylase () is an enzyme that catalyses the hydrolysis of starch (Latin ') into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large amounts of ...
, are important in many industries, including the paper, cosmetic, and food.
Chitin Chitin ( C8 H13 O5 N)n ( ) is a long-chain polymer of ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is probably the second most abundant polysaccharide in nature (behind only cellulose); an estimated 1 billion tons of chit ...
is a derivation of cellulose, possessing an
acetamide Acetamide (systematic name: ethanamide) is an organic compound with the formula CH3CONH2. It is the simplest amide derived from acetic acid. It finds some use as a plasticizer and as an industrial solvent. The related compound ''N'',''N''-dime ...
group instead of an –OH on one of its carbons. Acetimide group is deacetylated the polymer chain is then called
chitosan Chitosan is a linear polysaccharide composed of randomly distributed β-(1→4)-linked D-glucosamine (deacetylated unit) and ''N''-acetyl-D-glucosamine (acetylated unit). It is made by treating the chitin shells of shrimp and other crustacean ...
. Both of these cellulose derivatives are a major source of research for the biomedical and food industries. They have been shown to assist with
blood clotting Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechan ...
, have antimicrobial properties, and dietary applications. A lot of engineering and research is focusing on the degree of
deacetylation : In organic chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply '' acetates''. Deacetylation is the oppo ...
that provides the most effective result for specific applications.


Nucleic acids

Nucleic acids Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...
are macromolecules that consist of DNA and RNA which are biopolymers consisting of chains of biomolecules. These two molecules are the genetic code and template that make life possible. Manipulation of these molecules and structures causes major changes in function and expression of other macromolecules.
Nucleosides Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar ( ribose or 2'-deoxyribose) whereas a nucleo ...
are glycosylamines containing a nucleobase bound to either
ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally-occurring form, , is a component of the ribonucleotides from which RNA is built, and so this com ...
or deoxyribose sugar via a beta-glycosidic linkage. The sequence of the bases determine the genetic code.
Nucleotides Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules with ...
are nucleosides that are phosphorylated by specific
kinases In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
via a
phosphodiester bond In chemistry, a phosphodiester bond occurs when exactly two of the hydroxyl groups () in phosphoric acid react with hydroxyl groups on other molecules to form two ester bonds. The "bond" involves this linkage . Discussion of phosphodiesters is ...
. Nucleotides are the repeating structural units of nucleic acids. The nucleotides are made of a nitrogenous base, a pentose (ribose for RNA or deoxyribose for DNA), and three phosphate groups. See,
Site-directed mutagenesis Site-directed mutagenesis is a molecular biology method that is used to make specific and intentional mutating changes to the DNA sequence of a gene and any gene products. Also called site-specific mutagenesis or oligonucleotide-directed mutagenesi ...
,
recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be f ...
, and
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
s.


Lipids

Lipids Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids in ...
are biomolecules that are made up of
glycerol Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...
derivatives bonded with
fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...
chains.
Glycerol Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...
is a simple
polyol In organic chemistry, a polyol is an organic compound containing multiple hydroxyl groups (). The term "polyol" can have slightly different meanings depending on whether it is used in food science or polymer chemistry. Polyols containing two, thr ...
that has a formula of C3H5(OH)3. Fatty acids are long carbon chains that have a
carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyli ...
group at the end. The
carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon ma ...
chains can be either saturated with hydrogen; every carbon bond is occupied by a hydrogen atom or a single bond to another carbon in the carbon chain, or they can be unsaturated; namely, there are double bonds between the carbon atoms in the chain. Common fatty acids include
lauric acid Lauric acid, systematically dodecanoic acid, is a saturated fatty acid with a 12-carbon atom chain, thus having many properties of medium-chain fatty acids. It is a bright white, powdery solid with a faint odor of bay oil or soap. The salts and ...
,
stearic acid Stearic acid ( , ) is a saturated fatty acid with an 18-carbon chain. The IUPAC name is octadecanoic acid. It is a waxy solid and its chemical formula is C17H35CO2H. Its name comes from the Greek word στέαρ "''stéar''", which means ta ...
, and
oleic acid Oleic acid is a fatty acid that occurs naturally in various animal and vegetable fats and oils. It is an odorless, colorless oil, although commercial samples may be yellowish. In chemical terms, oleic acid is classified as a monounsaturated o ...
. The study and engineering of lipids typically focuses on the manipulation of lipid membranes and encapsulation. Cellular membranes and other biological membranes typically consist of a
phospholipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
membrane, or a derivative thereof. Along with the study of cellular membranes, lipids are also important molecules for energy storage. By utilizing encapsulation properties and
thermodynamic Thermodynamics is a branch of physics that deals with heat, work, and temperature, and their relation to energy, entropy, and the physical properties of matter and radiation. The behavior of these quantities is governed by the four laws of ...
characteristics, lipids become significant assets in structure and
energy In physics, energy (from Ancient Greek: ἐνέργεια, ''enérgeia'', “activity”) is the quantitative property that is transferred to a body or to a physical system, recognizable in the performance of work and in the form of ...
control when engineering molecules.


Of molecules


Recombinant DNA

Recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be f ...
are DNA biomolecules that contain genetic sequences that are not native to the organism's genome. Using recombinant techniques, it is possible to insert, delete, or alter a DNA sequence precisely without depending on the location of restriction sites. Recombinant DNA is used for a wide range of applications.


Method

The traditional method for creating recombinant DNA typically involves the use of
plasmids A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
in the host bacteria. The plasmid contains a genetic sequence corresponding to the recognition site of a restriction endonuclease, such as EcoR1. After foreign DNA fragments, which have also been cut with the same restriction endonuclease, have been inserted into host cell, the restriction endonuclease gene is expressed by applying heat, or by introducing a biomolecule, such as arabinose. Upon expression, the enzyme will cleave the plasmid at its corresponding recognition site creating sticky ends on the plasmid.
Ligases In biochemistry, a ligase is an enzyme that can catalyze the joining ( ligation) of two large molecules by forming a new chemical bond. This is typically via hydrolysis of a small pendant chemical group on one of the larger molecules or the enzy ...
then joins the sticky ends to the corresponding sticky ends of the foreign DNA fragments creating a recombinant DNA plasmid. Advances in
genetic engineering Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including ...
have made the modification of genes in microbes quite efficient allowing constructs to be made in about a weeks worth of time. It has also made it possible to modify the organism's genome itself. Specifically, use of the genes from the
bacteriophage lambda ''Enterobacteria phage λ'' (lambda phage, coliphage λ, officially ''Escherichia virus Lambda'') is a bacterial virus, or bacteriophage, that infects the bacterial species ''Escherichia coli'' (''E. coli''). It was discovered by Esther Leder ...
are used in recombination. This mechanism, known as recombineering, utilizes the three proteins Exo, Beta, and Gam, which are created by the genes exo, bet, and gam respectively. Exo is a double stranded DNA
exonuclease Exonucleases are enzymes that work by cleaving nucleotides one at a time from the end (exo) of a polynucleotide chain. A hydrolyzing reaction that breaks phosphodiester bonds at either the 3′ or the 5′ end occurs. Its close relative is ...
with 5' to 3' activity. It cuts the double stranded DNA leaving 3' overhangs. Beta is a protein that binds to single stranded DNA and assists
homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...
by promoting annealing between the homology regions of the inserted DNA and the chromosomal DNA. Gam functions to protect the DNA insert from being destroyed by native nucleases within the cell.


Applications

Recombinant DNA can be engineered for a wide variety of purposes. The techniques utilized allow for specific modification of genes making it possible to modify any biomolecule. It can be engineered for laboratory purposes, where it can be used to analyze genes in a given organism. In the pharmaceutical industry, proteins can be modified using recombination techniques. Some of these proteins include human
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism ...
. Recombinant insulin is synthesized by inserting the human insulin gene into '' E. coli'', which then produces insulin for human use. Other proteins, such as
human growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
,
factor VIII Factor VIII (FVIII) is an essential blood-clotting protein, also known as anti-hemophilic factor (AHF). In humans, factor VIII is encoded by the ''F8'' gene. Defects in this gene result in hemophilia A, a recessive X-linked coagulation disorder ...
, and hepatitis B vaccine are produced using similar means. Recombinant DNA can also be used for diagnostic methods involving the use of the
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
method. This makes it possible to engineer antigens, as well as the enzymes attached, to recognize different substrates or be modified for bioimmobilization. Recombinant DNA is also responsible for many products found in the agricultural industry.
Genetically modified food Genetically modified foods (GM foods), also known as genetically engineered foods (GE foods), or bioengineered foods are foods produced from organisms that have had changes introduced into their DNA using the methods of genetic engineering. Gene ...
, such as
golden rice Golden rice is a variety of rice (''Oryza sativa'') produced through genetic engineering to biosynthesize beta-carotene, a precursor of vitamin A, in the edible parts of the rice. It is intended to produce a fortified food to be grown and cons ...
, has been engineered to have increased production of
vitamin A Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably ...
for use in societies and cultures where dietary vitamin A is scarce. Other properties that have been engineered into crops include herbicide-resistance and insect-resistance.


Site-directed mutagenesis

Site-directed mutagenesis Site-directed mutagenesis is a molecular biology method that is used to make specific and intentional mutating changes to the DNA sequence of a gene and any gene products. Also called site-specific mutagenesis or oligonucleotide-directed mutagenesi ...
is a technique that has been around since the 1970s. The early days of research in this field yielded discoveries about the potential of certain chemicals such as bisulfite and aminopurine to change certain bases in a gene. This research continued, and other processes were developed to create certain nucleotide sequences on a gene, such as the use of restriction enzymes to fragment certain viral strands and use them as primers for bacterial plasmids. The modern method, developed by Michael Smith in 1978, uses an oligonucleotide that is complementary to a bacterial plasmid with a single base pair mismatch or a series of mismatches.


General procedure

Site directed mutagenesis is a valuable technique that allows for the replacement of a single base in an oligonucleotide or gene. The basics of this technique involve the preparation of a primer that will be a complementary strand to a wild type bacterial plasmid. This primer will have a base pair mismatch at the site where the replacement is desired. The primer must also be long enough such that the primer will anneal to the wild type plasmid. After the primer anneals, a DNA polymerase will complete the primer. When the bacterial plasmid is replicated, the mutated strand will be replicated as well. The same technique can be used to create a gene insertion or deletion. Often, an antibiotic resistant gene is inserted along with the modification of interest and the bacteria are cultured on an antibiotic medium. The bacteria that were not successfully mutated will not survive on this medium, and the mutated bacteria can easily be cultured.


Applications

Site-directed mutagenesis can be helpful for many different reasons. A single base-pair replacement will change the
codon The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
, potentially replacing an
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
in a protein. Mutagenesis can help determine the function of proteins and the roles of specific amino acids. If an amino acid near the active site is mutated, the kinetic parameters may change drastically, or the enzyme might behave differently. Another application of site-directed mutagenesis is exchanging an amino acid residue far from the active site with a
lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated − ...
residue or
cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, some ...
residue. These amino acids make it easier to covalently bond the enzyme to a solid surface, which allows for enzyme re-use and the use of enzymes in continuous processes. Sometimes, amino acids with non-natural functional groups (such as an aldehyde introduced through an aldehyde tag) are added to proteins.Peng Wua, Wenqing Shuia, Brian L. Carlsona, Nancy Hua, David Rabukaa, Julia Leea, and Carolyn R. Bertozzi (2009). "Site-specific chemical modification of recombinant proteins produced in mammalian cells by using the genetically encoded aldehyde tag". ''Proc. Natl. Acad. Sci U.S.A.'' 106 (9):3000-5. https://doi.org/10.1073/pnas.0807820106 These additions may be for ease of bioconjugation or to study the effects of amino acid changes on the form and function of the proteins. One example of how mutagenesis is used is found in the coupling of site-directed mutagenesis and PCR to reduce
interleukin-6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smoo ...
activity in cancerous cells. In another example, ''
Bacillus subtilis ''Bacillus subtilis'', known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus ''Bacillus ...
'' is used in site-directed mutagenesis, to secrete the enzyme
subtilisin Subtilisin is a protease (a protein-digesting enzyme) initially obtained from '' Bacillus subtilis''. Subtilisins belong to subtilases, a group of serine proteases that – like all serine proteases – initiate the nucleophilic attack on t ...
through the cell wall. Biomolecular engineers can purposely manipulate this gene to essentially make the cell a factory for producing whatever protein the insertion in the gene codes.


Bio-immobilization and bio-conjugation

Bio-immobilization and bio-conjugation is the purposeful manipulation of a biomolecule's mobility by chemical or physical means to obtain a desired property. Immobilization of biomolecules allows exploiting characteristics of the molecule under controlled environments. For example , the immobilization of glucose oxidase on calcium alginate gel beads can be used in a bioreactor. The resulting product will not need purification to remove the enzyme because it will remain linked to the beads in the column. Examples of types of biomolecules that are immobilized are enzymes, organelles, and complete cells. Biomolecules can be immobilized using a range of techniques. The most popular are physical entrapment, adsorption, and covalent modification. *Physical entrapment - the use of a polymer to contain the biomolecule in a matrix without chemical modification. Entrapment can be between lattices of polymer, known as gel entrapment, or within micro-cavities of synthetic fibers, known as fiber entrapment. Examples include entrapment of enzymes such as glucose oxidase in gel column for use as a
bioreactor A bioreactor refers to any manufactured device or system that supports a biologically active environment. In one case, a bioreactor is a vessel in which a chemical process is carried out which involves organisms or biochemically active substance ...
. Important characteristic with entrapment is biocatalyst remains structurally unchanged, but creates large diffusion barriers for substrates. *
Adsorption Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which a ...
- immobilization of biomolecules due to interaction between the biomolecule and groups on support. Can be physical adsorption, ionic bonding, or metal binding chelation. Such techniques can be performed under mild conditions and relatively simple, although the linkages are highly dependent upon pH, solvent and temperature. Examples include enzyme-linked immunosorbent assays. * Covalent modification- involves chemical reactions between certain functional groups and matrix. This method forms stable complex between biomolecule and matrix and is suited for mass production. Due to the formation of chemical bond to functional groups, loss of activity can occur. Examples of chemistries used are DCC coupling PDC coupling and EDC/NHS coupling, all of which take advantage of the reactive amines on the biomolecule's surface. Because immobilization restricts the biomolecule, care must be given to ensure that functionality is not entirely lost. Variables to consider are pH, temperature, solvent choice, ionic strength, orientation of active sites due to conjugation. For enzymes, the conjugation will lower the kinetic rate due to a change in the 3-dimensional structure, so care must be taken to ensure functionality is not lost. Bio-immobilization is used in technologies such as diagnostic
bioassay A bioassay is an analytical method to determine the concentration or potency of a substance by its effect on living animals or plants (''in vivo''), or on living cells or tissues(''in vitro''). A bioassay can be either quantal or quantitative, dir ...
s,
biosensor A biosensor is an analytical device, used for the detection of a chemical substance, that combines a biological component with a physicochemical detector. The ''sensitive biological element'', e.g. tissue, microorganisms, organelles, cell rece ...
s,
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
, and bioseparations. Interleukin (IL-6) can also be bioimmobilized on biosensors. The ability to observe these changes in IL-6 levels is important in diagnosing an illness. A cancer patient will have elevated IL-6 level and monitoring those levels will allow the physician to watch the disease progress. A direct immobilization of IL-6 on the surface of a biosensor offers a fast alternative to
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
.


Polymerase chain reaction

The
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...
(PCR) is a scientific technique that is used to replicate a piece of a DNA molecule by several orders of magnitude. PCR implements a cycle of repeated heated and cooling known as
thermal cycling Thermal analysis is a branch of materials science where the properties of materials are studied as they change with temperature. Several methods are commonly used – these are distinguished from one another by the property which is measured: * ...
along with the addition of DNA primers and DNA polymerases to selectively replicate the DNA fragment of interest. The technique was developed by Kary Mullis in 1983 while working for the Cetus Corporation. Mullis would go on to win the
Nobel Prize in Chemistry ) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
in 1993 as a result of the impact that PCR had in many areas such as
DNA cloning Molecular cloning is a set of experimental methods in molecular biology that are used to assemble recombinant DNA molecules and to direct their replication within host organisms. The use of the word ''cloning'' refers to the fact that the metho ...
,
DNA sequencing DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. T ...
, and gene analysis.


Biomolecular engineering techniques involved in PCR

A number of biomolecular engineering strategies have played a very important role in the development and practice of PCR. For instance a crucial step in ensuring the accurate replication of the desired DNA fragment is the creation of the correct DNA primer. The most common method of primer synthesis is by the
phosphoramidite A phosphoramidite (RO)2PNR2 is a monoamide of a phosphite diester. The key feature of phosphoramidites is their markedly high reactivity towards nucleophiles catalyzed by weak acids ''e.c''., triethylammonium chloride or 1''H''-tetrazole. In these ...
method. This method includes the biomolecular engineering of a number of molecules to attain the desired primer sequence. The most prominent biomolecular engineering technique seen in this
primer Primer may refer to: Arts, entertainment, and media Films * ''Primer'' (film), a 2004 feature film written and directed by Shane Carruth * ''Primer'' (video), a documentary about the funk band Living Colour Literature * Primer (textbook), a te ...
design method is the initial bioimmobilization of a nucleotide to a solid support. This step is commonly done via the formation of a covalent bond between the 3'-hydroxy group of the first nucleotide of the primer and the solid support material. Furthermore, as the DNA primer is created certain functional groups of nucleotides to be added to the growing
primer Primer may refer to: Arts, entertainment, and media Films * ''Primer'' (film), a 2004 feature film written and directed by Shane Carruth * ''Primer'' (video), a documentary about the funk band Living Colour Literature * Primer (textbook), a te ...
require blocking to prevent undesired side reactions. This blocking of functional groups as well as the subsequent de-blocking of the groups, coupling of subsequent nucleotides, and eventual cleaving from the solid support are all methods of manipulation of biomolecules that can be attributed to biomolecular engineering. The increase in interleukin levels is directly proportional to the increased death rate in breast cancer patients. PCR paired with Western blotting and ELISA help define the relationship between cancer cells and IL-6.


Enzyme-linked immunosorbent assay (ELISA)

Enzyme-linked immunosorbent assay The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...
is an assay that utilizes the principle of
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of t ...
-
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
recognition to test for the presence of certain substances. The three main types of
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
tests which are indirect
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
, sandwich
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
, and competitive
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
all rely on the fact that
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
have an affinity for only one specific
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
. Furthermore, these
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
s or
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
can be attached to
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s which can react to create a colorimetric result indicating the presence of the
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of t ...
or
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
of interest. Enzyme linked immunosorbent assays are used most commonly as diagnostic tests to detect HIV antibodies in blood samples to test for HIV,
human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantatio ...
molecules in urine to indicate pregnancy, and
Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on it ...
antibodies in blood to test patients for tuberculosis. Furthermore,
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
is also widely used as a toxicology screen to test people's serum for the presence of illegal drugs.


Techniques involved in ELISA

Although there are three different types of solid state
enzyme-linked immunosorbent assays The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presenc ...
, all three types begin with the bioimmobilization of either an
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of t ...
or
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
to a surface. This bioimmobilization is the first instance of biomolecular engineering that can be seen in
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
implementation. This step can be performed in a number of ways including a covalent linkage to a surface which may be coated with protein or another substance. The bioimmobilization can also be performed via hydrophobic interactions between the molecule and the surface. Because there are many different types of
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
s used for many different purposes the biomolecular engineering that this step requires varies depending on the specific purpose of the
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
. Another biomolecular engineering technique that is used in
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
development is the
bioconjugation Bioconjugation is a chemical strategy to form a stable covalent link between two molecules, at least one of which is a biomolecule. Function Recent advances in the understanding of biomolecules enabled their application to numerous fields lik ...
of an enzyme to either an
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of t ...
or
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
depending on the type of
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
. There is much to consider in this
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
bioconjugation Bioconjugation is a chemical strategy to form a stable covalent link between two molecules, at least one of which is a biomolecule. Function Recent advances in the understanding of biomolecules enabled their application to numerous fields lik ...
such as avoiding interference with the
active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate ( binding site) ...
of the
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
as well as the
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of t ...
binding site in the case that the
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of t ...
is conjugated with
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
. This
bioconjugation Bioconjugation is a chemical strategy to form a stable covalent link between two molecules, at least one of which is a biomolecule. Function Recent advances in the understanding of biomolecules enabled their application to numerous fields lik ...
is commonly performed by creating crosslinks between the two molecules of interest and can require a wide variety of different reagents depending on the nature of the specific molecules. Interleukin (IL-6) is a signaling protein that has been known to be present during an immune response. The use of the sandwich type
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
quantifies the presence of this cytokine within spinal fluid or bone marrow samples.


Applications and fields


In industry

Biomolecular engineering is an extensive discipline with applications in many different industries and fields. As such, it is difficult to pinpoint a general perspective on the Biomolecular engineering profession. The biotechnology industry, however, provides an adequate representation. The biotechnology industry, or biotech industry, encompasses all firms that use biotechnology to produce goods or services or to perform biotechnology research and development. In this way, it encompasses many of the industrial applications of the biomolecular engineering discipline. By examination of the biotech industry, it can be gathered that the principal leader of the industry is the United States, followed by France and Spain. It is also true that the focus of the biotechnology industry and the application of biomolecular engineering is primarily clinical and medical. People are willing to pay for good health, so most of the money directed towards the biotech industry stays in health-related ventures.


Scale-up

Scaling up a process involves using data from an experimental-scale operation (model or pilot plant) for the design of a large (scaled-up) unit, of commercial size. Scaling up is a crucial part of commercializing a process. For example,
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism ...
produced by genetically modified
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
bacteria was initialized on a lab-scale, but to be made commercially viable had to be scaled up to an industrial level. In order to achieve this scale-up a lot of lab data had to be used to design commercial sized units. For example, one of the steps in insulin production involves the crystallization of high purity glargin insulin. In order to achieve this process on a large scale we want to keep the Power/Volume ratio of both the lab-scale and large-scale crystallizers the same in order to achieve homogeneous mixing. We also assume the lab-scale crystallizer has geometric similarity to the large-scale crystallizer. Therefore, P/V α Ni3di3
where di= crystallizer impeller diameter
Ni= impeller rotation rate


Related industries


Bioengineering

A broad term encompassing all engineering applied to the life sciences. This field of study utilizes the principles of
biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary ...
along with engineering principles to create marketable products. Some
bioengineering Biological engineering or bioengineering is the application of principles of biology and the tools of engineering to create usable, tangible, economically-viable products. Biological engineering employs knowledge and expertise from a number o ...
applications include: *
Biomimetics Biomimetics or biomimicry is the emulation of the models, systems, and elements of nature for the purpose of solving complex human problems. The terms "biomimetics" and "biomimicry" are derived from grc, βίος (''bios''), life, and μίμησ ...
- The study and development of synthetic systems that mimic the form and function of natural biologically produced substances and processes. *
Bioprocess engineering Bioprocess engineering, also biochemical engineering, is a specialization of chemical engineering or biological engineering. It deals with the design and development of equipment and processes for the manufacturing of products such as agriculture, ...
- The study and development of process equipment and optimization that aids in the production of many products such as food and
pharmaceuticals A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and re ...
. * Industrial microbiology - The implementation of
microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in old ...
s in the production of industrial products such as food and
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
s. Another common application of industrial microbiology is the treatment of wastewater in chemical plants via utilization of certain
microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in old ...
s.


Biochemistry

Biochemistry is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemical processes govern all living organisms and living processes and the field of biochemistry seeks to understand and manipulate these processes.


Biochemical engineering

*
Biocatalysis Biocatalysis refers to the use of living (biological) systems or their parts to speed up (catalyze) chemical reactions. In biocatalytic processes, natural catalysts, such as enzymes, perform chemical transformations on organic compounds. Both enz ...
– Chemical transformations using
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s. * Bioseparations – Separation of biologically active molecules. *
Thermodynamics Thermodynamics is a branch of physics that deals with heat, work, and temperature, and their relation to energy, entropy, and the physical properties of matter and radiation. The behavior of these quantities is governed by the four laws ...
and Kinetics (chemistry) – Analysis of reactions involving cell growth and biochemicals. *
Bioreactor A bioreactor refers to any manufactured device or system that supports a biologically active environment. In one case, a bioreactor is a vessel in which a chemical process is carried out which involves organisms or biochemically active substance ...
design and analysis – Design of reactors for performing biochemical transformations.


Biotechnology

*
Biomaterials A biomaterial is a substance that has been engineered to interact with biological systems for a medical purpose, either a therapeutic (treat, augment, repair, or replace a tissue function of the body) or a diagnostic one. As a science, biomateria ...
– Design, synthesis and production of new materials to support cells and tissues. *
Genetic engineering Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including ...
– Purposeful manipulation of the genomes of organisms to produce new phenotypic traits. * Bioelectronics,
Biosensor A biosensor is an analytical device, used for the detection of a chemical substance, that combines a biological component with a physicochemical detector. The ''sensitive biological element'', e.g. tissue, microorganisms, organelles, cell rece ...
and
Biochip In molecular biology, biochips are engineered substrates ("miniaturized laboratories") that can host large numbers of simultaneous biochemical reactions. One of the goals of biochip technology is to efficiently screen large numbers of biological ...
– Engineered devices and systems to measure, monitor and control biological processes. *
Bioprocess engineering Bioprocess engineering, also biochemical engineering, is a specialization of chemical engineering or biological engineering. It deals with the design and development of equipment and processes for the manufacturing of products such as agriculture, ...
– Design and maintenance of cell-based and enzyme-based processes for the production of fine chemicals and pharmaceuticals.


Bioelectrical engineering

Bioelectrical engineering involves the electrical fields generated by living cells or organisms. Examples include the
electric potential The electric potential (also called the ''electric field potential'', potential drop, the electrostatic potential) is defined as the amount of work energy needed to move a unit of electric charge from a reference point to the specific point in ...
developed between muscles or nerves of the body. This discipline requires knowledge in the fields of
electricity Electricity is the set of physical phenomena associated with the presence and motion of matter that has a property of electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as describe ...
and
biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary ...
to understand and utilize these concepts to improve or better current bioprocesses or technology. * Bioelectrochemistry - Chemistry concerned with electron/proton transport throughout the cell * Bioelectronics - Field of research coupling biology and electronics


Biomedical engineering

Biomedical engineering is a sub category of
bioengineering Biological engineering or bioengineering is the application of principles of biology and the tools of engineering to create usable, tangible, economically-viable products. Biological engineering employs knowledge and expertise from a number o ...
that uses many of the same principles but focuses more on the medical applications of the various engineering developments. Some applications of
biomedical engineering Biomedical engineering (BME) or medical engineering is the application of engineering principles and design concepts to medicine and biology for healthcare purposes (e.g., diagnostic or therapeutic). BME is also traditionally logical sciences ...
include: *
Biomaterial A biomaterial is a substance that has been engineered to interact with biological systems for a medical purpose, either a therapeutic (treat, augment, repair, or replace a tissue function of the body) or a diagnostic one. As a science, biomateria ...
s - Design of new materials for implantation in the human body and analysis of their effect on the body. * Cellular engineering – Design of new cells using
recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be f ...
and development of procedures to allow normal cells to adhere to artificial implanted
biomaterial A biomaterial is a substance that has been engineered to interact with biological systems for a medical purpose, either a therapeutic (treat, augment, repair, or replace a tissue function of the body) or a diagnostic one. As a science, biomateria ...
s *
Tissue engineering Tissue engineering is a biomedical engineering discipline that uses a combination of Cell (biology), cells, engineering, Materials science, materials methods, and suitable biochemistry, biochemical and physicochemical factors to restore, maintai ...
– Design of new tissues from the basic biological building blocks to form new tissues * Artificial organs – Application of tissue engineering to whole organs *
Medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to re ...
– Imaging of tissues using CAT scan, MRI,
ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies ...
,
x-ray An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10  nanometers, corresponding to frequencies in the range 30&nb ...
or other technologies *Medical Optics and Lasers – Application of lasers to medical diagnosis and treatment * Rehabilitation engineering – Design of devices and systems used to aid disabled people *Man-machine interfacing - Control of surgical robots and remote diagnostic and therapeutic systems using eye tracking, voice recognition and muscle and brain wave controls *
Human factors and ergonomics Human factors and ergonomics (commonly referred to as human factors) is the application of psychological and physiological principles to the engineering and design of products, processes, and systems. Four primary goals of human factors learnin ...
– Design of systems to improve human performance in a wide range of applications


Chemical engineering

Chemical engineering is the processing of raw materials into chemical products. It involves preparation of raw materials to produce reactants, the chemical reaction of these reactants under controlled conditions, the separation of products, the recycle of byproducts, and the disposal of wastes. Each step involves certain basic building blocks called "unit operations," such as extraction, filtration, and distillation. These unit operations are found in all chemical processes. Biomolecular engineering is a subset of Chemical Engineering that applies these same principles to the processing of chemical substances made by living organisms.


Education and programs

Newly developed and offered undergraduate programs across the United States, often coupled to the chemical engineering program, allow students to achieve a B.S. degree. According to
ABET The ABET (incorporated as the Accreditation Board for Engineering and Technology, Inc.) is a non-governmental organization that accredits post-secondary education programs in applied and natural sciences, computing, engineering and engineering ...
(Accreditation Board for Engineering and Technology), biomolecular engineering curricula "must provide thorough grounding in the basic sciences including chemistry, physics, and biology, with some content at an advanced level… ndengineering application of these basic sciences to design, analysis, and control, of chemical, physical, and/or biological processes." Common curricula consist of major engineering courses including transport, thermodynamics, separations, and kinetics, with additions of
life sciences This list of life sciences comprises the branches of science that involve the scientific study of life – such as microorganisms, plants, and animals including human beings. This science is one of the two major branches of natural science, th ...
courses including biology and biochemistry, and including specialized biomolecular courses focusing on cell biology, nano- and biotechnology, biopolymers, etc.


See also

*
Biomimetics Biomimetics or biomimicry is the emulation of the models, systems, and elements of nature for the purpose of solving complex human problems. The terms "biomimetics" and "biomimicry" are derived from grc, βίος (''bios''), life, and μίμησ ...
* Biopharmaceuticals *
Bioprocess engineering Bioprocess engineering, also biochemical engineering, is a specialization of chemical engineering or biological engineering. It deals with the design and development of equipment and processes for the manufacturing of products such as agriculture, ...
* List of biomolecules * Molecular engineering


References


Further reading


Biomolecular engineering at interfaces
(article)
Recent Progress in Biomolecular Engineering
* Biomolecular sensors (alk. paper)


External links


AIChE International Conference on Biomolecular Engineering
{{Engineering fields Biological processes Biotechnology