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Auxotrophy ( grc, αὐξάνω "to increase"; ''τροφή'' "nourishment") is the inability of an organism to synthesize a particular
organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...
required for its growth (as defined by
IUPAC The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...
). An auxotroph is an organism that displays this characteristic; ''auxotrophic'' is the corresponding adjective. Auxotrophy is the opposite of prototrophy, which is characterized by the ability to synthesize all the compounds needed for growth. Prototrophic cells (also referred to as the '
wild type The wild type (WT) is the phenotype of the typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard "normal" allele at a locus, in contrast to that produced by a non-standard, "m ...
') are self sufficient producers of all required metabolites (e.g.
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 am ...
s,
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 include ...
s,
cofactors Cofactor may also refer to: * Cofactor (biochemistry), a substance that needs to be present in addition to an enzyme for a certain reaction to be catalysed * A domain parameter in elliptic curve cryptography, defined as the ratio between the order ...
), while auxotrophs require to be on medium with the metabolite that they cannot produce. For example saying a cell is
methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...
auxotrophic means that it would need to be on a medium containing methionine or else it would not be able to replicate. In this example this is because it is unable to produce its own methionine (methionine auxotroph). However, a prototroph or a methionine prototrophic cell would be able to function and replicate on a medium with or without methionine. Replica plating is a technique that transfers colonies from one plate to another in the same spot as the last plate so the different media plates can be compared side by side. It is used to compare the growth of the same colonies on different plates of media to determine which environments the bacterial colony can or cannot grow in (this gives insight to possible auxotrophic characteristics. The method of
replica plating Replica plating is a microbiological technique in which one or more secondary Petri plates containing different solid (agar-based) selective growth media (lacking nutrients or containing chemical growth inhibitors such as antibiotics) are inocul ...
implemented by
Joshua Lederberg Joshua () or Yehoshua ( ''Yəhōšuaʿ'', Tiberian: ''Yŏhōšuaʿ,'' lit. 'Yahweh is salvation') ''Yēšūaʿ''; syr, ܝܫܘܥ ܒܪ ܢܘܢ ''Yəšūʿ bar Nōn''; el, Ἰησοῦς, ar , يُوشَعُ ٱبْنُ نُونٍ '' Yūšaʿ ...
and
Esther Lederberg Esther Miriam Zimmer Lederberg (December 18, 1922 – November 11, 2006) was an American microbiologist and a pioneer of bacterial genetics. She discovered the bacterial virus λ and the bacterial fertility factor F, devised the first impl ...
included auxotrophs that were temperature-sensitive; that is, their ability to synthesize was temperature-dependent. (Auxotrophs are usually not temperature-dependent. They can also depend on other factors.) It is also possible that an organism is auxotrophic to more than just one organic compound that it requires for growth.


Applications


Genetics

In
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
, a
strain Strain may refer to: Science and technology * Strain (biology), variants of plants, viruses or bacteria; or an inbred animal used for experimental purposes * Strain (chemistry), a chemical stress of a molecule * Strain (injury), an injury to a mu ...
is said to be auxotrophic if it carries a
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
that renders it unable to synthesize an essential compound. For example, a
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
mutant with an inactivated
uracil Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by ...
synthesis pathway gene is a uracil auxotroph (e.g., if the yeast
Orotidine 5'-phosphate decarboxylase Orotidine 5'-phosphate decarboxylase (OMP decarboxylase) or orotidylate decarboxylase is an enzyme involved in pyrimidine biosynthesis. It catalyzes the decarboxylation of orotidine monophosphate (OMP) to form uridine monophosphate (UMP). The fu ...
gene is inactivated, the resultant strain is a uracil auxotroph). Such a strain is unable to synthesize uracil and will only be able to grow if uracil can be taken up from the environment. This is the opposite of a uracil prototroph, or in this case a
wild-type The wild type (WT) is the phenotype of the typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard "normal" allele at a locus, in contrast to that produced by a non-standard, "m ...
strain, which can still grow in the absence of uracil. Auxotrophic genetic markers are often used in
molecular genetics Molecular genetics is a sub-field of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the ...
; they were famously used in
Beadle A beadle, sometimes spelled bedel, is an official of a church or synagogue who may usher, keep order, make reports, and assist in religious functions; or a minor official who carries out various civil, educational, or ceremonial duties on the ...
and Tatum's
Nobel prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
-winning work on the
one gene-one enzyme hypothesis 1 (one, unit, unity) is a number representing a single or the only entity. 1 is also a numerical digit and represents a single unit of counting or measurement. For example, a line segment of ''unit length'' is a line segment of length 1. I ...
, connecting mutations of genes to protein mutations. This then allows for biosynthetic or biochemical pathway mapping that can help determine which enzyme or enzymes are mutated and dysfunctional in the auxotrophic strains of bacteria being studied. Researchers have used strains of '' E. coli'' auxotrophic for specific amino acids to introduce non-natural amino acid analogues into
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 ...
. For instance cells auxotrophic for the amino acid phenylalanine can be grown in media supplemented with an analogue such as para-azido phenylalanine. Many living things, including humans, are auxotrophic for large classes of compounds required for growth and must obtain these compounds through diet (see
vitamin A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an Nutrient#Essential nutrients, essential micronutrient that an organism needs in small quantities for the proper functioning of its ...
,
essential nutrient A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...
,
essential amino acid An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life form ...
,
essential fatty acid Essential fatty acids, or EFAs, are fatty acids that humans and other animals must ingest because the body requires them for good health but cannot synthesize them. Only two fatty acids are known to be essential for humans: alpha-linolenic ac ...
). The complex pattern of evolution of vitamin auxotrophy across the
eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
tree of life is intimately connected with the interdependence between organisms.


The Mutagenicity test (or Ames test)

The Salmonella Mutagenesis test ( Ames test) uses multiple strains of ''
Salmonella typhimurium ''Salmonella enterica'' subsp. ''enterica'' is a subspecies of ''Salmonella enterica'', the rod-shaped, flagellated, aerobic, Gram-negative bacterium. Many of the pathogenic serovars of the ''S. enterica'' species are in this subspecies, includi ...
'' that are auxotrophic to
histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...
to test whether a given chemical can cause
mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
by observing its auxotrophic property in response to an added chemical compound. The mutation a chemical substance or compound causes is measured by applying it to the bacteria on a plate containing histidine then moving the bacteria to a new plate without sufficient histidine for continual growth. If the substance does not mutate the genome of the bacteria from auxotrophic to histidine back to prototrophic to histidine, then the bacteria would not show growth on the new plate. So by comparing the ratio of the bacteria on the new plate to the old plate and the same ratio for the control group, it is possible to quantify how mutagenic a substance is, or rather, how likely it is to cause mutations in DNA. A chemical is considered positive for Ames test if it causes mutations increasing the observed reversion rate and negative if presents similar to the control group. There is a normal, but small, number of revertant colonies expected when an auxotrophic bacteria is plated on a media without the metabolite it needs because it could mutate back to prototrophy. The chances of this are low and therefore cause very small colonies to be formed. If a mutagenic substance is added, however, the number of revertants would be visibly higher than without the mutagenic substance. The Ames test, basically, is considered positive if a substance increases chance of mutation in the DNA of the bacteria enough to cause a quantifiable difference in the revertants of the mutagen plate and the control group plate. Negative Ames test means the possible mutagen DID not cause increase in revertants and positive Ames test signifies that the possible mutagen DID increase the chance of mutation. These mutagenic effects on bacteria are researched as a possible indicator of the same effects on larger organisms, like humans. It is suggested that if a mutation can arise in bacterial DNA under presence of a mutagen then the same effect would occur for larger organisms causing cancer. A negative Ames test result could suggest that the substance is not a mutagen and would not cause tumor formation in living organisms. However only few of the positive Ames Test resulting chemicals were considered insignificant when tested in larger organisms but the positive Ames test for bacteria still could not be conclusively linked to expression of cancer in larger organisms. While it can be a possible determinant of tumors for living organisms, humans, animals, and so on, more studies must be completed to come to a conclusion.


Auxotrophy-based methods to incorporate unnatural amino acids into proteins and proteomes

A large number of unnatural amino acids, which are similar to their canonical counterparts in shape, size and chemical properties, are introduced into the recombinant proteins by means of auxotrophic expression hosts. For example, methionine (Met) or tryptophan (Trp) auxotrophic ''Escherichia coli'' strains can be cultivated in a defined minimal medium. In this experimental setup it is possible to express recombinant proteins whose canonical Trp and Met residues are completely substituted with different medium-supplemented related analogs. This methodology leads to a new form of protein engineering, which is not performed by codon manipulation at the DNA level (e.g. oligonucleotide-directed mutagenesis), but by
codon reassignment Codon reassignment is the biological process via which the genetic code of a cell is changed as a response to the environment. It may be caused by alternative tRNA aminoacylation, in which the cell modifies the target aminoacid of some particular ...
s at the level of protein translation under efficient selective pressure. Therefore, the method is referred as selective pressure incorporation (SPI). No organism studied so far encodes other amino acids than the canonical twenty; two additional canonical amino acids (selenocysteine, pyrrolysine) are inserted into proteins by recoding translation termination signals. This boundary can be crossed by adaptive laboratory evolution of metabolically stable auxotrophic microbial strains. For example, the first clearly successful attempt to evolve ''Escherichia coli'' that can survive solely on the unnatural amino acid thieno ,2-byrrolyl) alanine as the only substitute for tryptophan was made in 2015.


In popular culture

The 1993 film ''
Jurassic Park ''Jurassic Park'', later also referred to as ''Jurassic World'', is an American science fiction media franchise created by Michael Crichton and centered on a disastrous attempt to create a theme park of cloned dinosaurs. It began in 1990 when ...
'' (based on the 1990
Michael Crichton John Michael Crichton (; October 23, 1942 – November 4, 2008) was an American author and filmmaker. His books have sold over 200 million copies worldwide, and over a dozen have been adapted into films. His literary works heavily feature tech ...
novel of the same name) features
dinosaur Dinosaurs are a diverse group of reptiles of the clade Dinosauria. They first appeared during the Triassic period, between 243 and 233.23 million years ago (mya), although the exact origin and timing of the evolution of dinosaurs is t ...
s that were genetically altered so that they could not produce the amino acid
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 −C ...
. This was known as the "lysine contingency" and was supposed to prevent the
cloned Cloning is the process of producing individual organisms with identical or virtually identical DNA, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction. In the field of biotechnology, c ...
dinosaurs from surviving outside the park, forcing them to be dependent on lysine supplements provided by the park's veterinary staff. In reality, no animals are capable of producing lysine (it is an
essential amino acid An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life form ...
).


See also

*
Autotroph An autotroph or primary producer is an organism that produces complex organic compounds (such as carbohydrates, fats, and proteins) using carbon from simple substances such as carbon dioxide,Morris, J. et al. (2019). "Biology: How Life Works", ...
* Bradytroph


Footnotes

{{Reflist


External links


"Regulation of endosomal clathrin and retromer-mediated endosome to Golgi retrograde transport by the J-domain protein RME-8" - The EMBO Journal

"Pleiotropic effects of purine auxotrophy inRhizobium meliloti on cell surface molecules" - Springerlink

"Auxotrophy and Organic Compounds in the Nutrition of Marine Phytoplankton"
Molecular genetics