Polyhydroxyalkanoates or PHAs are

polyester Polyester is a category of polymers that contain the ester functional group in every repeat unit of their main chain. As a specific material, it most commonly refers to a type called polyethylene terephthalate (PET). Polyesters include natural ...

s produced in nature by numerous microorganisms, including through

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

fermentation Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food ...

sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or double ...

s or

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. When produced by bacteria they serve as both a source of energy and as a carbon store. More than 150 different

monomer In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification Mo ...

s can be combined within this family to give materials with extremely different properties. These plastics are biodegradable and are used in the production of

bioplastics Bioplastics are plastic materials produced from renewable biomass sources, such as vegetable fats and oils, corn starch, straw, woodchips, sawdust, recycled food waste, etc. Some bioplastics are obtained by processing directly from natural bio ...

. They can be either

thermoplastic A thermoplastic, or thermosoft plastic, is any plastic polymer material that becomes pliable or moldable at a certain elevated temperature and solidifies upon cooling. Most thermoplastics have a high molecular weight. The polymer chains associate ...

elastomer An elastomer is a polymer with viscoelasticity (i.e. both viscosity and elasticity) and with weak intermolecular forces, generally low Young's modulus and high failure strain compared with other materials. The term, a portmanteau of ''elastic p ...

ic materials, with

melting point The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depends ...

s ranging from 40 to 180 °C. The mechanical properties and

biocompatibility Biocompatibility is related to the behavior of biomaterials in various contexts. The term refers to the ability of a material to perform with an appropriate host response in a specific situation. The ambiguity of the term reflects the ongoing de ...

of PHA can also be changed by blending, modifying the surface or combining PHA with other polymers, enzymes and inorganic materials, making it possible for a wider range of applications.

Biosynthesis

To induce PHA production in a laboratory setting, a culture of a micro-organism such as '' Cupriavidus necator'' can be placed in a suitable medium and fed appropriate nutrients so that it multiplies rapidly. Once the population has reached a substantial level, the nutrient composition can be changed to force the micro-organism to synthesize PHA. The yield of PHA obtained from the intracellular granule inclusions can be as high as 80% of the organism's dry weight. The biosynthesis of PHA is usually caused by certain deficiency conditions (e.g. lack of macro elements such as phosphorus, nitrogen, trace elements, or lack of oxygen) and the excess supply of carbon sources. However, the prevalence of PHA production within either a mono-culture or a set of mixed-microbial organisms can also simply be dependent on overall nutrient limitation, not just macro elements. This is especially the case in the 'feast/famine' cycle method for induction of PHA production, wherein carbon is periodically added and depleted to cause famine, which encourages cells to produce PHA during 'feast' as a storage method for periods of famine. Polyesters are deposited in the form of highly refractive granules in the cells. Depending upon the microorganism and the cultivation conditions, homo- or

copolyester Copolyester forms when modifications are made to polyesters, which are combinations of diacids and diols. For example, by introducing other diacids, such as isophthalic acid (IPA), or other diols, such as cyclohexane dimethanol (CHDM) to the polyes ...

s with different hydroxyalkanoic acids are generated. PHA granules are then recovered by disrupting the cells. Recombinant ''

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 ''Bacillu ...

'' str. pBE2C1 and ''Bacillus subtilis'' str. pBE2C1AB were used in production of polyhydroxyalkanoates (PHA) and it was shown that they could use

malt Malt is germinated cereal grain that has been dried in a process known as " malting". The grain is made to germinate by soaking in water and is then halted from germinating further by drying with hot air. Malted grain is used to make beer, wh ...

waste as carbon source for lower cost of PHA production. PHA synthases are the key enzymes of PHA biosynthesis. They use the coenzyme A - thioester of (r)-hydroxy fatty acids as substrates. The two classes of PHA synthases differ in the specific use of hydroxy fatty acids of short or medium chain length. The resulting PHA is of the two types: *Poly (HA SCL) from hydroxy fatty acids with short chain lengths including three to five carbon atoms are synthesized by numerous bacteria, including '' Cupriavidus necator'' and ''

Alcaligenes latus ''Azohydromonas lata'' is a gram-negative, hydrogen-using bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic ...

'' ( PHB). *Poly (HA MCL) from hydroxy fatty acids with medium chain lengths including six to 14 carbon atoms, can be made for example, by ''

Pseudomonas putida ''Pseudomonas putida'' is a Gram-negative, rod-shaped, saprotrophic soil bacterium. Based on 16S rRNA analysis, ''P. putida'' was taxonomically confirmed to be a ''Pseudomonas'' species (''sensu stricto'') and placed, along with several other ...

''. A few bacteria, including ''

Aeromonas hydrophila ''Aeromonas hydrophila'' is a heterotrophic, Gram-negative, rod-shaped bacterium mainly found in areas with a warm climate. This bacterium can be found in fresh or brackish water. It can survive in Wikt:aerobic, aerobic and Hypoxia (environmen ...

'' and ''

Thiococcus pfennigii ''Thiococcus'' is a Gram-negative, non‐motile, obligately phototrophic and strictly anaerobic genus of bacteria from the family of Chromatiaceae with one known species ('' Thiococcus pfennigii''). ''Thiococcus pfennigii'' was first isolated fr ...

'', synthesize copolyester from the above two types of hydroxy fatty acids, or at least possess enzymes that are capable of part of this synthesis. Another even larger scale synthesis can be done with the help of soil organisms. For lack of nitrogen and phosphorus they produce a kilogram of PHA per three kilograms of sugar. The simplest and most commonly occurring form of PHA is the fermentative production of poly-beta-hydroxybutyrate (poly-3-hydroxybutyrate, P3HB), which consists of 1000 to 30000 hydroxy fatty acid monomers.

Industrial production

In the industrial production of PHA, the polyester is extracted and purified from the bacteria by optimizing the conditions of microbial fermentation of

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, using ...

, or

vegetable oil Vegetable oils, or vegetable fats, are oils extracted from seeds or from other parts of fruits. Like animal fats, vegetable fats are ''mixtures'' of triglycerides. Soybean oil, grape seed oil, and cocoa butter are examples of seed oils, or fat ...

. In the 1980s,

Imperial Chemical Industries Imperial Chemical Industries (ICI) was a British chemical company. It was, for much of its history, the largest manufacturer in Britain. It was formed by the merger of four leading British chemical companies in 1926. Its headquarters were at M ...

developed poly(3-hydroxybutyrate-''co''-3-hydroxyvalerate) obtained via fermentation that was named "Biopol". It was sold under the name "Biopol" and distributed in the U.S. by

Monsanto The Monsanto Company () was an American agrochemical and agricultural biotechnology corporation founded in 1901 and headquartered in Creve Coeur, Missouri. Monsanto's best known product is Roundup, a glyphosate-based herbicide, developed in th ...

and later

Metabolix Yield10 Bioscience (formerly Metabolix, Inc.) is a company developing new technologies to achieve improvements in crop yield to enhance global food security. History Founded in 1992, with the help of a licensing agreement with Massachusetts Inst ...

. As raw material for the fermentation, carbohydrates such as glucose and sucrose can be used, but also vegetable oil or glycerine from biodiesel production. Researchers in industry are working on methods with which transgenic crops will be developed that express PHA synthesis routes from bacteria and so produce PHA as energy storage in their tissues. Several companies are working to develop methods of producing PHA from waste water, including

Veolia Veolia Environnement S.A., branded as Veolia, is a French transnational company with activities in three main service and utility areas traditionally managed by public authorities – water management, waste management and energy services. It pr ...

subsidiary Anoxkaldnes. and start-ups, Micromidas, Mango Materials, Full Cycle Bioplastics, Newlight an
Paques Biomaterials
PHAs are processed mainly via injection molding, extrusion and extrusion bubbles into films and hollow bodies.

Material properties

PHA polymers are thermoplastic, can be processed on conventional processing equipment, and are, depending on their composition, ductile and more or less elastic. They differ in their properties according to their chemical composition (homo-or copolyester, contained hydroxy fatty acids). They are UV stable, in contrast to other bioplastics from polymers such as

polylactic acid Polylactic acid, also known as poly(lactic acid) or polylactide (PLA), is a thermoplastic polyester with backbone formula or , formally obtained by condensation of lactic acid with loss of water (hence its name). It can also be prepared by rin ...

, partial ca. temperatures up to , and show a low permeation of water. The

crystallinity Crystallinity refers to the degree of structural order in a solid. In a crystal, the atoms or molecules are arranged in a regular, periodic manner. The degree of crystallinity has a big influence on hardness, density, Transparency and translucen ...

can lie in the range of a few to 70%. Processability, impact strength and flexibility improves with a higher percentage of

valerate Valeric acid or pentanoic acid is a straight-chain alkyl carboxylic acid with the chemical formula . Like other low-molecular-weight carboxylic acids, it has an unpleasant odor. It is found in the perennial flowering plant ''Valeriana officina ...

in the material. PHAs are soluble in halogenated solvents such

chloroform Chloroform, or trichloromethane, is an organic compound with chemical formula, formula Carbon, CHydrogen, HChlorine, Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to ...

dichloromethane Dichloromethane (DCM or methylene chloride, methylene bichloride) is an organochlorine compound with the formula . This colorless, volatile liquid with a chloroform-like, sweet odour is widely used as a solvent. Although it is not miscible with ...

dichloroethane Dichloroethane can refer to either of two isomeric organochlorides with the molecular formula C2H4Cl2: * 1,1-Dichloroethane (ethylidene chloride) * 1,2-Dichloroethane (ethylene dichloride) See also *Dichloroethene *Difluoroethane Difluoroethane m ...

. PHB is similar in its material properties to

polypropylene Polypropylene (PP), also known as polypropene, is a thermoplastic polymer used in a wide variety of applications. It is produced via chain-growth polymerization from the monomer propylene. Polypropylene belongs to the group of polyolefins and ...

(PP), has a good resistance to moisture and aroma barrier properties. Polyhydroxybutyric acid synthesized from pure PHB is relatively brittle and stiff. PHB copolymers, which may include other fatty acids such as beta-hydroxyvaleric acid, may be elastic.

Applications

Image:Poly-3-hydroxyvalerat.svg, Structure of poly-3-hydroxyvalerate (PHV) Image:Poly-4-hydroxybutyrat.svg, Structure of poly-4-hydroxybutyrate (P4HB) Due to its

biodegradability Biodegradation is the breakdown of organic matter by microorganisms, such as bacteria and fungi. It is generally assumed to be a natural process, which differentiates it from composting. Composting is a human-driven process in which biodegradati ...

and potential to create

bioplastic Bioplastics are plastic materials produced from renewable biomass sources, such as vegetable fats and oils, corn starch, straw, woodchips, sawdust, recycled food waste, etc. Some bioplastics are obtained by processing directly from natural ...

s with novel properties, much interest exists to develop the use of PHA-based materials. PHA fits into the

green economy A green economy is an economy that aims at reducing environmental risks and ecological scarcities, and that aims for sustainable development without degrading the environment. It is closely related with ecological economics, but has a more politi ...

as a means to create plastics from non-fossil fuel sources. Furthermore, active research is being carried out for the

biotransformation Biotransformation is the biochemical modification of one chemical compound or a mixture of chemical compounds. Biotransformations can be conducted with whole cells, their lysates, or purified enzymes. Increasingly, biotransformations are effected w ...

upcycling Upcycling, also known as creative reuse, is the process of transforming by-products, waste materials, useless, or unwanted products into new materials or products perceived to be of greater quality, such as artistic value or environmental value ...

" of plastic waste (e.g.,

polyethylene terephthalate Polyethylene terephthalate (or poly(ethylene terephthalate), PET, PETE, or the obsolete PETP or PET-P), is the most common thermoplastic polymer resin of the polyester family and is used in fibres for clothing, containers for liquids and foods ...

and

polyurethane Polyurethane (; often abbreviated PUR and PU) refers to a class of polymers composed of organic chemistry, organic units joined by carbamate (urethane) links. In contrast to other common polymers such as polyethylene and polystyrene, polyurethan ...

) into PHA using ''

'' bacteria. A PHA copolymer called PHBV (poly(3-hydroxybutyrate-co-3-hydroxyvalerate)) is less stiff and tougher, and it may be used as packaging material. In June 2005, US company

, Inc. received the US

Presidential Green Chemistry Challenge Award Green chemistry, also called sustainable chemistry, is an area of chemistry and chemical engineering focused on the design of products and processes that minimize or eliminate the use and generation of hazardous substances. While environmental che ...

(small business category) for their development and commercialisation of a cost-effective method for manufacturing PHAs. There are potential applications for PHA produced by micro-organisms within the agricultural, medical and pharmaceutical industries, primarily due to their biodegradability. Fixation and orthopaedic applications have included sutures, suture fasteners,

meniscus Meniscus may refer to: *Meniscus (anatomy), crescent-shaped fibrocartilaginous structure that partly divides a joint cavity *Meniscus (liquid) The meniscus (plural: ''menisci'', from the Greek for "crescent") is the curve in the upper surface ...

repair devices,

rivet A rivet is a permanent mechanical fastener. Before being installed, a rivet consists of a smooth cylindrical shaft with a head on one end. The end opposite to the head is called the ''tail''. On installation, the rivet is placed in a punched ...

s, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins (including bone.lling augmentation material),

adhesion barrier An adhesion barrier is a medical implant that can be used to reduce abnormal internal scarring (adhesions) following surgery by separating the internal tissues and organs while they heal. Surgeons have realized that proper surgical technique is cr ...

stent In medicine, a stent is a metal or plastic tube inserted into the lumen of an anatomic vessel or duct to keep the passageway open, and stenting is the placement of a stent. A wide variety of stents are used for different purposes, from expandab ...

s, guided tissue repair/regeneration devices, articular

cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...

repair devices, nerve guides,

tendon A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle to bone. It is able to transmit the mechanical forces of muscle contraction to the skeletal system without sacrificing its ability ...

repair devices,

atrial septal defect Atrial septal defect (ASD) is a congenital heart defect in which blood flows between the atria (upper chambers) of the heart. Some flow is a normal condition both pre-birth and immediately post-birth via the foramen ovale; however, when this d ...

repair devices, pericardial patches, bulking and filling agents,

vein Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated b ...

valves,

bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...

scaffolds, meniscus regeneration devices,

ligament A ligament is the fibrous connective tissue that connects bones to other bones. It is also known as ''articular ligament'', ''articular larua'', ''fibrous ligament'', or ''true ligament''. Other ligaments in the body include the: * Peritoneal li ...

and tendon grafts,

ocular Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and con ...

cell implants, spinal fusion cages, skin substitutes,

dural Dural is a suburb of Sydney, in the state of New South Wales, Australia 36 kilometres north-west of the Sydney central business district in the local government areas of Hornsby Shire and The Hills Shire. Dural is part of the Hills District. ...

substitutes, bone graft substitutes, bone dowels, wound dressings, and

hemostat A hemostat (also called a hemostatic clamp, arterial forceps, or pean after Jules-Émile Péan) is a surgical tool used in many surgical procedures to control bleeding. For this reason, it is common in the initial phases of surgery for the initia ...

Biosynthesis

Industrial production

Material properties

Applications

References

Further reading