HYDROXYBUTYRIC ACID COPOLYMER

Hydroxybutyric acid can also be directly incorporated [38], though some of it reacts with the corresponding enoyl-CoA. A more likely pathway proposed is via succinate semialdehyde, succinate, pyruvate, and acetyl-CoA, derived from 4-hydroxybutyrate, generally leading to a copolymer of 3-hydroxybutyryl and 4-hydroxybutyryl monomers from 4-hydroxybutyric acid [39]. 

PI IB/V, an scl- copolymer (Fig. 7.2B) produced by Alcaligenes eutrophus (since reclassified as Ralstonia eutropha) from propionic acid and glucose. This new polymer was tougher than PFIB and had a lower processing temperature making it more appealing to industry. Ultimately, this polymer was marketed under the trade name Biopol. In 1988, Doi and coworkers found that a new scZ-PHA copolymer of PHB-co-4-hydroxybutyrate (PHB/4HB Fig. 7.2C) could be synthesized from 4-hydroxybutyric acid or y-butyrolactone (Doi et al., 1988 Kunioka et al., 1989). 

Another example where metabolic pathway engineering has made a dramatic impact is in the biodegradable polymer field. The polymer of this family most widely studied is poly-P-hydroxybutyrate (PHB) (46). Another member of the PHA family commercialized by Imperial Chemical Industries (ICI), which later became Zeneca under the trade name Biopol, is a copolymer consisting of p-hydroxybutyric acid and P-hydroxyvaleric acid. This biodegradable polymer was first used in plastic shampoo bottles by the Wella Corporation [198]. In the early part of 1996, the Biopol product line, was purchased from Zeneca by the Monsanto Company. 

Hydroxybutyric acid-hydroxyvaleric acid copolymer membranes were treated with ozone and grafted with acrylic acid. The membranes were further grafted with chitosan or chitooligosaccharide via esterification and immobilised with hyalmonic acid. Antibacterial activities were investigated. Surface properties were characterised using a water contact angle goniometer. 26 refs. 

PCL was also degraded to 6-hydroxyhexanoic acid during enzymatic hydrolysis by Lipase Asahi derived from Chromobacterium viscosum and Hp-ase F derived from Rhizopus niveus [74]. In another study formation of oligomers during biotic hydrolysis of PCL was shown by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) [50]. Enzymatic degradation of copolymers of 3-hydroxybutyric acid (3HB) and... 

Synthetic or man-made, e.g., PVAl, CA, polylactams e.g., polycaprolactam), polyglycols (e.g., polyethylene glycol), poly(aspartic acid), poly(butylene succinate-co-adipate), as well as poly(3-hydroxy butyrate) or PHB, poly(P-hydroxybutyric acid) or PHBA, poly(hydroxy-valerate) or PHV, poly(lactic acid) or PLA, polyCglycolic acid), polyglycolides, polybu-tyric acid, their copolymers and mixtures. 

Polymers derived from renewable resources (biopolymers) are broadly classified according to the method of production (1) Polymers directly extracted/ removed from natural materials (mainly plants) (e.g. polysaccharides such as starch and cellulose and proteins such as casein and wheat gluten), (2) polymers produced by "classical" chemical synthesis from renewable bio-derived monomers [e.g. poly(lactic acid), poly(glycolic acid) and their biopolyesters polymerized from lactic/glycolic acid monomers, which are produced by fermentation of carbohydrate feedstock] and (3) polymers produced by microorganisms or genetically transformed bacteria [e.g. the polyhydroxyalkanoates, mainly poly(hydroxybutyrates) and copolymers of hydroxybutyrate (HB) and hydroxyvalerate (HV)] [4]. 

Mexon is a synthetic single-fiber thread with slow absorption characteristics, made of a copolymer of glycolic acid and trimethyl carbonate. Three weeks after implantation it retains about 55% of its initial resistance complete absorption takes place after 26-30 weeks. The products of hydrolytic thread decomposition are carbon dioxide, -hydroxybutyric acid, and glycolic acid. 

Gursel, L and Hasirci, V. Properties and drug release behaviour of poly(3-hydroxy-butyric acid) and various poly(3-hydroxybutyrate-hydroxyvalerate) copolymer microcapsules. J. M croewca/jsw/., 1995,12(2), 185-193. 

An important development of orthopaedic implants has been the development of artificial composites, which when combined with biomolecules will induce osteogenesis. The properties of hydroxyapatite (HA) materials have been studied over the years with a view to increasing elasticity. Because biocompatibility has been a problem when HA has been combined with various polyethylenes and polysulphones, polyhydroxyalkanoates (PHAs) and its chemical composites, a polymer of hydroxybutyric acid (PHB), copolymers of hydroxybutyric acid and... 

The metabolic pathways involved in the synthesis of P(3HB-co-4HB) from 4-hydroxybutyric acid are shown in Fig. 2.4. Transferase or thiokinase catalyzes the conversion of 4-hydroxybutyric acid into 4HB-CoA, which is then used as the substrate by the PHA synthase in the polymerization reaction. The catabolism of 4-hydroxybutyric acid also leads to the formation of intermediates such as 3-hydroxybutyryl-CoA, resulting in the accumulation of P(3HB-co-4HB) copolymer. The main catabolic pathway for 4HB is probably via succinic acid semialdehyde and succinic acid pathways, which are catalyzed by 4HB dehydrogenase and succinic acid semialdehyde dehydrogenase (Valentin et al. 1995 Lutke-Eversloh and Steinbiichel 1999). All precursor substrates for the generation of 4HB monomers are first converted into 4HB-CoA, which is the immediate substrate for PHA synthase. 

Recently, a random copolymer of 3HB and 4-hydroxybutyrate (4HB) (Figure Ic) is produced by A. eutrophus from 4-hydroxybutyric acid [9,10], or Y-bulyrolactone [11,12], This copolyester can be made in a wide variety of materials, from hard crystalline plastic to very elastic rubber, depending on the copolymer composition. More recently, the... 

PHAs containing as monomers hydroxyaUcanoic acids different from hydroxyalkanoates have also been reported (Saito and Doi 1994 Schmack et al. 1998 Choi et al. 1999 Amirul et al. 2008). These polymers, which belong to both scl-PHAs and mcl-PHAs, have as a structural peculiarity an elongated backbone (Fig. 2). Among these UnPHAs, those copolymers containing as repeating units (/ )-3-hydroxybutyric acid and 4-hydroxybutyric acid poly[(/ )-3-hydroxybu-tyrate-co -hydroxybutyrate], P(3HB HB) are the paradigmatic examples. 

The microbial biosynthesis of P(3HB-4HB) copolymers was achieved using different nutritional strategies. Most of them are based on the carbon sources used to feed the cultures (butyric acid and different sugars, or a single carbon source structurally related to butyric acid such as 4-hydroxybutyric acid, y-butyrolactone or 1,4 butanediol Saito and Doi 1994 Kunioka et al. 1989). 

Shuai X-T, Jedlinski Z, Luo Q, Farhod N (2000) Synthesis of novel block copolymers of poly(3-hydroxybutyric acid) with poly(ethylene glycol) through anionic polymerizeition. Chin J Polym Sci 18 19-23... 

Abe H, Doi Y (1996) Enzymatic and environmental degradation of racemic poly(3-hydroxybutyric acid)s with different stereoregularities. Macromolecules 29 8683-8688 Abe H, Doi Y, Aoki H, Akehata T (1998) Solid-state structures and enzymatic degradabilities for melt-crystallized films of copolymers of (f )-3-hydroxybutyiic acid with different hydroxyal-kanoic acids. Macromolecules 31 1791-1797... 

Ravenelle F, Marchessault RH (2002) One-step synthesis of amphiphilic diblock copolymers from bacterial poly([/J]-3-hydroxybutyric acid). Biomacromolecules 3 1057-1064 Ravenelle F, Marchessault RH (2003) Self-assembly of poly([R]-3-hydroxybutyric aaA)-block-poly(ethylene glycol) diblock copolymers. Biomacromolecules 4 856-858 Renard E, Langlois V, Guerin P (2007) Chemical modifications of bacterial polyesters from stability to controlled degradation of resulting polymers. Corros Eng Sci Technol 42300-42310... 

The degree of crystallinity of solvent cast copolymer films decrease from 60 to 18% when the fraction of 3-hydroxyhexanoic acid is increased from 0 to 25 niol-%. This finding suggests that the 3-hydroxyhexanoic acid units are excluded from the crystalline phase of 3-hydroxybutyric acid. The rates of enzymatic erosion increase markedly with the increase of 3-hydroxyhexanoic acid the... 

Polymers in the group of polyesters, specifically the family of polyflactic acid) (PLA), polyfglycolic acid) (PGA), and copolymers of lactic and glycolic acids (PLGAs), as well as poly(P-hydroxybutyric acid) (PHB) most closely fulfilled the criteria outlined above, including biocompatibility, processability, and controlled degradation [8]. These polymers, many descendant of absorbable suture materials developed a couple of decades ago, were approved for in vivo use by the Food... 

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