Polyhydroxyalkanoates or PHAs are polyesters produced in nature by numerous microorganisms, including through

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

fermentation Fermentation is a type of anaerobic metabolism which harnesses the redox potential of the reactants to make adenosine triphosphate (ATP) and organic end products. Organic molecules, such as glucose or other sugars, are catabolized and reduce ...

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 Glucose is a sugar with the Chemical formula#Molecular formula, molecul ...

s or

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

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

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

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. They can be either

thermoplastic A thermoplastic, or thermosoftening 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 as ...

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

ic materials, with

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

s ranging from 40 to 180 °C. The mechanical properties and biocompatibility 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 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 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 copolyesters 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 ''Bacill ...

'' 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 any cereal grain that has been made to germinate by soaking in water and then stopped from germinating further by drying with hot air, a process known as "malting". Malted grain is used to make beer, whisky, malted milk, malt vinegar, ...

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'' ( 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''. A few bacteria, including '' Aeromonas hydrophila'' and '' Thiococcus pfennigii'', 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 oly(3-hydroxybutyrate), P(3HB) 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 sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

, or

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

. In the 1980s,

Imperial Chemical Industries Imperial Chemical Industries (ICI) was a British Chemical industry, chemical company. It was, for much of its history, the largest manufacturer in Britain. Its headquarters were at Millbank in London. ICI was listed on the London Stock Exchange ...

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 and later Metabolix. 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 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, partial ca. temperatures up to , and show a low permeation of water. The crystallinity can lie in the range of a few to 70%. Processability, impact strength and flexibility improves with a higher percentage of valerate in the material. PHAs are soluble in halogenated solvents such

chloroform Chloroform, or trichloromethane (often abbreviated as TCM), is an organochloride with the formula and a common solvent. It is a volatile, colorless, sweet-smelling, dense liquid produced on a large scale as a precursor to refrigerants and po ...

, dichloromethane or dichloroethane. 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 Propene, propylene. Polypropylene belongs to the group of polyolefin ...

(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 and potential to create

bioplastic Bioplastics are plastic materials produced from renewable biomass sources. Timeline of plastic development, Historically, bioplastics made from natural materials like shellac or Celluloid, cellulose had been the first plastics. Since the end of ...

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 environmental degradation, degrading the environment. It is closely related with ecological econ ...

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

plastic waste Plastic pollution is the accumulation of plastic objects and particles (e.g. plastic bottles, bags and microbeads) in the Earth's environment that adversely affects humans, wildlife and their habitat. Plastics that act as pollutants are cate ...

(e.g., polyethylene terephthalate and

polyurethane Polyurethane (; often abbreviated PUR and PU) is 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, polyurethane term ...

) into PHA using '' Pseudomonas putida'' 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 Metabolix, Inc. received the US Presidential Green Chemistry Challenge Award (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 repair devices, rivets, 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 barriers, stents, guided tissue repair/regeneration devices, articular

cartilage Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...

repair devices, nerve guides,

tendon A tendon or sinew is a tough band of fibrous connective tissue, dense fibrous connective tissue that connects skeletal muscle, muscle to bone. It sends the mechanical forces of muscle contraction to the skeletal system, while withstanding tensi ...

repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices,

ligament A ligament is a type of fibrous connective tissue in the body that connects bones to other bones. It also connects flight feathers to bones, in dinosaurs and birds. All 30,000 species of amniotes (land animals with internal bones) have liga ...

and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats.

Biosynthesis

Industrial production

Material properties

Applications

References

Further reading