Polyhydroxybutyrate degradation

In Europe, interest has centered particularly on polyhydroxybutyrate, which can be made into films for packaging as well as into molded items. The polymer degrades within 4 weeks in landfills, both by ester hydrolysis and by an ElcB elimination reaction of the oxygen atom p to the carbonyl group. The use of polyhydroxybutyrate is limited at present by its cost—about four times that of polypropylene. 

Aliphatic polyesters based on monomers other than a-hydroxyalkanoic acids have also been developed and evaluated as drug delivery matrices. These include the polyhydroxybutyrate and polyhydroxy valerate homo- and copolymers developed by Imperial Chemical Industries (ICI) from a fermentation process and the polycaprolactones extensively studied by Pitt and Schindler (14,15). The homopolymers in these series of aliphatic polyesters are hydrophobic and crystalline in structure. Because of these properties, these polyesters normally have long degradation times in vivo of 1-2 years. However, the use of copolymers and in the case of polycaprolactone even polymer blends have led to materials with useful degradation times as a result of changes in the crystallinity and hydrophobicity of these polymers. An even larger family of polymers based upon hydroxyaliphatic acids has recently been prepared by bacteria fermentation processes, and it is anticipated that some of these materials may be evaluated for drug delivery as soon as they become commercially available. 

There are two principal ways by which polymer chains can be hydrolyzed, passively by chemical hydrolysis or actively by enzymatic reaction. The latter method is most important for naturally occurring polymers such as polysaccharides and polyfhydroxy alkanoate)s, e.g., polyhydroxybutyrate and polyhydroxyvaler-ate [121,125]. Many synthetic aliphatic polyesters utilized in medical applications degrade mainly by pure hydrolysis [121]. 

Polyhydroxybutyrate Biodegradable polyester used in degradable plastic products. 

Tian J, Sinskey AJ, Stubbe J (2005) Kinetic studies of polyhydroxybutyrate granule formation in Wautersia eutrvpha H16 by transmission electron microscopy. J Bacteriol 187 3814—3824 TokiwaY, CalabiaBP (2004) Degradation of microbial polyesters. Biotechnol Lett 26 1181-1189 Tokiwa Y, Ugwu CU (2007) Biotechnological production of (R)-3-hydroxybutyric add monomer. J Biotechnol 132 264—272... 

Besides the common polyhydroxybutyrate (PHB), other polymers of this class are produced by a variety of organisms such as poly-4-hydroxybutyrate, PHV, and polyhy-droxyhexanoate. PHV is a naturally occurring bacterial polyester, which was first isolated by Wallen and coworkers [172,173]. Also, PHV/PHB copolymers have been studied to make a wide range of thermally processable polyesters, which exhibit the necessary long-term degradation profile required for a degradable fracture fixation device [174]. 

Knowles, J., Hastings, G., Ohta, H., Niwa, S., Boeree, N. Development of a degradable composite for orthopaedic use in vivo biomechanical and histological evaluation of two bioactive degradable composites based on the polyhydroxybutyrate polymer. Biomaterials 13, 491 96 (1992)... 

Figure 19 A molecular surface representation of the PHA depolymerase from Penicillium funiculosum cemmQ on the mouth of the crevice. The positions of solvent-exposed hydrophobic residues (purple), as well as polar (green) and catalytic triad (cyan) residues, are indicated. A model of the 3HB trimer bound in the crevice is shown as a yellow stick model. Reproduced with permission from Hisano, T. Kasuya, K. Tezuka, Y. etal. The Crystal Structure of Polyhydroxybutyrate Depolymerase from Penicillium funiculosum Provides Insights into the Recognition and Degradation of Biopolyesters, J. Mol. Biol. 2006, 356, 993, Copyright (2006), with permission from Elsevier.

Due to the differences between the physical structures of the intracellular native granules and extracellular denatured PHA, intracellular PhaZ is unable to hydrolyse extracellular PHA, and extracellular PhaZ cannot hydrolyse intracellular PHA [14]. The enzymatic degradation of P(3HB) is known as a heterogeneous reaction because the polyhydroxybutyrate (PHB) depolymerase is water-soluble, whereas the P(3HB) polymer is water-insoluble. Therefore, the enzymatic degradation of P(3HB) involves two steps, namely adsorption and hydrolysis. During adsorption, the enzyme is attached to the surface of P(3HB) via the binding domain of the polymer. This is followed by hydrolysis of the polymer chain at the active site of the enzyme [5]. 

Gordeyev SA, Nekrasov YPJ (1999) Processing and mechanical properties of oriented poly(beta-hyioxybutyrate) fibers. Mater Sd Lett 18 1691-1692 Hisano T, Kasuya K, Tezuka Y, Ishii N, Kobayashi T, Shiraki M, Oroudjev M, Hansma H, Iwata T, Doi Y, Saito T, Mild K (2006) The crystal structure of polyhydroxybutyrate depolymerase from Penicilliumjuniculosum provides insights into the recognition and degradation of biopolyesters. J Mol Biol 356 993-1004... 

Handrick R, Reinhardt S, Schultheiss D, Reichart T, Schuler D, Jendrossek V, Jendrossek D (2004a) Unraveling the function of Rhodospirillum rubrum activator of polyhydroxybutyrate (PHB)degradation the activator is a PHB-granule-bound protein (phasin). J Bacteriol 186 2466-2475... 

Numata K, Sato S, Fujita M, Tsuge T, Iwata T, Doi Y (2007) Adsorption effects of poly(hydroxybutyric add) depolymerase on chain-folding surface of polyester single crystals revealed by mutant enzyme and frictional force microscopy. Polym Degrad Stab 92 176-183 Ohura T, Kasuya K, Doi Y (1999) Cloning and characterization of the polyhydroxybutyrate depolymerase gene of Pseudomonas stutzeri and analysis of the function of substrate-binding domains. Appl Environ Microbiol 65 189-197... 

Pouton CW, Majid MIA, Notarianni LJ (1988) Degradation of polyhydroxybutyrate and related copolymers. Proc Int Symp Control Release Bioact Mater 15 182-183 Ramsay BA, Saracovan I, Ramsay JA, Marchessault RH (1994) A method for the isolation of microorganism producing extracellular long-side-chain poly(P-hydroxyalkanoate) depolymerase). J Environ Polym Degrad 2 1-7... 

Polyhydroxyalkanoates, Polyhydroxybutyrate, History, Bacterial synthesis. Chemical synthesis. Genetic engineering. Mechanical properties. Thermal transitions. Crystallization, Plasticizers, Thermal degradation. Processing, Applications... 

---