Polyhydroxyalkanoates
Encyclopedia
Polyhydroxyalkanoates or PHAs are linear polyester
Polyester
Polyester is a category of polymers which contain the ester functional group in their main chain. Although there are many polyesters, the term "polyester" as a specific material most commonly refers to polyethylene terephthalate...

s produced in nature by bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

l fermentation
Fermentation (biochemistry)
Fermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. In contrast, respiration is where electrons are donated to an exogenous electron acceptor, such as oxygen,...

 of sugar
Sugar
Sugar is a class of edible crystalline carbohydrates, mainly sucrose, lactose, and fructose, characterized by a sweet flavor.Sucrose in its refined form primarily comes from sugar cane and sugar beet...

 or lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

s. They are produced by the bacteria to store carbon and energy. More than 150 different monomer
Monomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...

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

They can be either thermoplastic
Thermoplastic
Thermoplastic, also known as a thermosoftening plastic, is a polymer that turns to a liquid when heated and freezes to a very glassy state when cooled sufficiently...

 or elastomer
Elastomer
An elastomer is a polymer with the property of viscoelasticity , generally having notably low Young's modulus and high yield strain compared with other materials. The term, which is derived from elastic polymer, is often used interchangeably with the term rubber, although the latter is preferred...

ic materials, with melting point
Melting point
The melting point of a solid 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 on pressure and is usually specified at standard atmospheric pressure...

s ranging from 40 to 180 °C.

The mechanical and biocompatibility
Biocompatibility
Biocompatibility is related to the behavior of biomaterials in various contexts. The term may refer to specific properties of a material without specifying where or how the material is used , or to more empirical clinical success of a whole device in...

 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 produce PHA, a culture of a micro-organism such as Alcaligenes eutrophus
Alcaligenes eutrophus
Alcaligenes eutrophus is a bacterial species that naturally produces polyhydroxyalkanoates . PHAs are a broad type of biodegradable polymers that can be used for biodegradable plastics. A...

is 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 is changed to force the micro-organism to synthesize PHA. The yield of PHA obtained from the intracellular 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.

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 hydroxyalkanic acids are generated. PHAs granules are then recovered by disrupting the cells

Recombinants Bacillus subtilis
Bacillus subtilis
Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium commonly found in soil. A member of the genus Bacillus, B. subtilis is rod-shaped, and has the ability to form a tough, protective endospore, allowing the organism to tolerate...

str. pBE2C1 and Bacillus subtilis str. pBE2C1AB were used in production of polyhydroxyalkanoates (PHA) and it was shown that they could use malt
Malt
Malt is germinated cereal grains that have been dried in a process known as "malting". The grains are made to germinate by soaking in water, and are then halted from germinating further by drying with hot air...

 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 hydroxyfattyacids 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 Ralstonia eutropha
    Ralstonia eutropha
    Ralstonia eutropha is a gram-negative soil bacterium of the betaproteobacteria class.-Taxonomy:R. eutropha has gone through a series of name changes. In the first half of the 20th century many microorganisms were isolated for their ability to utilize hydrogen. Hydrogen metabolizing...

    and Alcaligenes latus (PHB
    Polyhydroxybutyrate
    Polyhydroxybutyrate is a polyhydroxyalkanoate , a polymer belonging to the polyesters class that was first isolated and characterized in 1925 by French microbiologist Maurice Lemoigne. PHB is produced by microorganisms apparently in response to conditions of physiological stress...

    ).

  • Poly (HA MCL) from hydroxy fatty acids with middle chain lengths including six to 14 carbon atoms, can be made for example, by Pseudomonas putida
    Pseudomonas putida
    Pseudomonas putida is a gram-negative rod-shaped saprotrophic soil bacterium. Based on 16S rRNA analysis, P. putida has been placed in the P. putida group, to which it lends its name....

    .


A few bacteria, including Aeromonas hydrophila
Aeromonas hydrophila
Aeromonas hydrophila is a heterotrophic, Gram-negative, rod shaped bacterium, mainly found in areas with a warm climate. This bacterium can also be found in fresh, salt, marine, estuarine, chlorinated, and un-chlorinated water. Aeromonas hydrophila can survive in aerobic and anaerobic...

and Thiococcus pfennigii, synthesize copolyester, from the above two types of hydroxy fatty acids or at least possess enzymes that are part of this building are capable of.

Another even large scale synthesis can be done with the help of soil organisms. For lack of nitrogen and phosphorus they produce from three kilograms of sugar a kilogram of PHA.
The simplest and most commonly occurring form of PHA is the fermentative production of poly-beta-hydroxybutyrate
Polyhydroxybutyrate
Polyhydroxybutyrate is a polyhydroxyalkanoate , a polymer belonging to the polyesters class that was first isolated and characterized in 1925 by French microbiologist Maurice Lemoigne. PHB is produced by microorganisms apparently in response to conditions of physiological stress...

) (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 sugar or glucose.

The British chemical company Imperial Chemical Industries (ICI), developed in the 1980s years fermentatively created copolyester produced from 3-hydroxybutyrate and 3-Hydroxyvalerianacid. It was sold under the name "Biopol." It was distributed in the U.S. from the company Monsanto and Metabolix and has been further developed by them.

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. Another group of researchers at Micromidas Inc. is working to develop methods of producing PHA from municipal waste water.

PHAs are processed mainly via injection molding, extrusion and extrusion bubbles into films and hollow bodies.

Some PHA producers include:
  • Metabolix, US
  • Tepha, US
  • Greenbio, Tianjin, China
  • PHB Industrial SA, or Biocycle, Brazil
  • Tianan Biologic Material Co, Ltd Ningbo, China
  • Biomer
  • Bio-on

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
Ultraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...

 stable, in contrast to other bioplastics from polymers such as polylactic acid
Polylactic acid
Poly or polylactide is a thermoplastic aliphatic polyester derived from renewable resources, such as corn starch , tapioca products or sugarcanes...

, partial ca. temperatures up to , [1] and show a low permeation of water.

The crystallinity
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 diffusion. In a gas, the relative positions of the atoms or...

 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.

PHB is similar in its material properties to polypropylene (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-hydroxyvaleriate acid, may be elastic.

Applications

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, a 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 medical and pharmaceutical industries, primarily due to their biodegradability.

Fixation and orthopaedic applications have included sutures, suture fasteners, meniscus
Meniscus
The meniscus is the curve in the upper surface of a liquid close to the surface of the container or another object, caused by surface tension. It can be either convex or concave. A convex meniscus occurs when the molecules have a stronger attraction to each other than to the material of the...

 repair devices, rivet
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 the head is called the buck-tail. On installation the rivet is placed in a punched or pre-drilled hole, and the tail is upset, or bucked A rivet...

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
Adhesion barrier
An adhesion barrier is a medical implant that can be used to reduce abnormal internal scarring following surgery by separating the internal tissues and organs while they heal....

s, stent
Stent
In the technical vocabulary of medicine, a stent is an artificial 'tube' inserted into a natural passage/conduit in the body to prevent, or counteract, a disease-induced, localized flow constriction. The term may also refer to a tube used to temporarily hold such a natural conduit open to allow...

s, guided tissue repair/regeneration devices, articular cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...

 repair devices, nerve guides, tendon
Tendon
A tendon is a tough band of fibrous connective tissue that usually connects muscle to bone and is capable of withstanding tension. Tendons are similar to ligaments and fasciae as they are all made of collagen except that ligaments join one bone to another bone, and fasciae connect muscles to other...

 repair devices, atrial septal defect
Atrial septal defect
Atrial septal defect is a form of congenital heart defect that enables blood flow between the left and right atria via the interatrial septum. The interatrial septum is the tissue that divides the right and left atria...

 repair devices, pericardial patches, bulking and filling agents, vein
Vein
In the circulatory system, veins are blood vessels 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 blood to the heart...

 valves, bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

 scaffolds, meniscus regeneration devices, ligament
Ligament
In anatomy, the term ligament is used to denote any of three types of structures. Most commonly, it refers to fibrous tissue that connects bones to other bones and is also known as articular ligament, articular larua, fibrous ligament, or true ligament.Ligament can also refer to:* Peritoneal...

 and tendon grafts, ocular
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...

 cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostat
Hemostat
A hemostat , is a vital surgical tool used in almost any surgical procedure, usually to control bleeding. Therefore, it is not uncommon to see the initial incision lined with hemostats closing blood vessels awaiting ligation during the initial phases of surgery...

s.

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