4- Hydroxybutyrate , monomer

The PHA degradation pathway as described in most bacteria studied begins with the depolymerization of PHA to D-3-hydroxybutyrate monomers by PHA depolymerase (encoded by phaZ). Extracellular and intracellular PHA degradation have been described (Jendrossek and Handrick 2002) for utilization of PHAs present in the environment or accumulated in PHA granules, respectively (Tanio et al. 1982 Saegusa et al. 2001 Jendrossek and Handrick 2002 Pbtter and Steinbiichel 2005). 

Figure 1. SCL-PHA production from non-related carbon sources. A. The tricarboxylic acid cycle. B. Poly-3-hydroxybutyrate [P(3HB)] monomer supply via the fatty acid biosynthesis enzymes, FabD, FabH, and FabG. C. P(3HB) monomer supply mediated by the beta-ketothiolase enzymes, PhaA or BktB, and the NADPH-reductase, PhaB. D. Poly-3-hydroxyvalerate (P3HV) monomer supply mediated by threonine deaminase (IlvA), pyruvate dehydrogenase, BktB, and PhaB. E. Poly-4-hydroxybutyrate monomer supply mediated by succinate dehydrogenase (SucD), 4-hydroxybutyrate dehydrogenase (4HbD), and acetyl transferase (Catl or Cat2).

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]. 

Comonomers, such as 3-hydroxyvalerate (3HV, ethylene R-unit (-CH2-CH3) in Fig. 1) and 4-hydroxybutyrate, have been incorporated in the PHB chains using specific additives in the growth medium of the bacteria [21-25]. It has been shown by nuclear magnetic resonance (NMR) studies that poly(3HB-co-3HV) has a statistically random distribution of the monomer units throughout a range of compositions varying from 0 to 90 mol % 3HV [23-26]. 

All purified poly(HA) depolymerases are specific for either poly(HASCL) or poly(HAMCL). Even a poly(3HB) depolymerase of S. exfoliatus K10, a strain that degrades both poly(3HB) and poly(3HO), is specific for poly(HASCL) [49]) indicating at least one additional depolymerase with specificity for poly(HAMCL) in S. exfoliatus. Experiments with copolymers consisting of 3-hydroxybutyrate and 3-hydroxyhexanoate and A.faecalis T1 poly(3HB) depolymerase are in agreement with the results obtained with poly(HASCL) and poly(HAMCL) the depolymerase was not able to hydrolyze ester bonds between two 3HAMCL monomers and between 3-hydroxybutyrate and 3-hydroxyhexanoate [50]. 

Carboxvalkvlation of Propylene Oxide. These reagents were also used in a similar carboxyalkylation scheme to prepare methyl 3-hydroxybutyrate by reaction with propylene oxide (Equation 3). This might represent a way to prepare substitute 1,3 diols(48) following reduction of the ester or reactive monomers by pyrolys is/dehydration. 

Another interesting example of lactones are the p-hydroxyalkanoates, whose ROP affords poly(p-hydroxyalkanoate)s (PHAs), a class of aliphatic polyesters naturally produced by bacteria (Fig. 3) [12, 13]. Poly(3-(R)-hydroxybutyrate) (PHB) is a typical example. PHB is a stiff thermoplastic material with relatively poor impact strength, but the incorporation of other monomers can improve the mechanical properties. 

Poly-B-Hydroxybutyrate. It has been shown (11,12,13) that poly-B-hydroxybutyrate (PHB) is a head-to-tail polyester based on the monomer J) (-)-B-hydroxybutyric acid which leads to an optically active polymer having the formula ... 

The polymerization of lactones with tin alkoxides is thought to follow the co-ordination-insertion mechanism[77a]. The ring-opening of the monomer proceeds through acyl-oxygen cleavage with retention of the configuration. Tin(IV) complexes have been used to produce predominantly syndiotactic poly((3-hy-droxybutyrate) [78,79],macrocyclic poly((3-hydroxybutyrate) [80],poly(e-CL), and polylactide [77,76,81]. 

PHB and P(HB-co-HV) have several merits as matrices for controlled drug delivery [107,109]. Their biosynthetic production excludes the use of solvents, initiators, or catalysts that could, if not properly removed from the biomedical device, pose a toxicological hazard to the patient. The materials are enzymatically as well as hydrolytically degradable. Biocompatibility does not seem to be a problem the monomer D-(-)-3-hydroxybutyrate is in fact a normal constituent of blood [231]. The ease of crystallization of PHB during precipitation makes entrapment of the drug difficult [107]. Hence, copolymers with HV have been more popular for drug formulation than the pure PHB. 

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