3-Hydroxyalkanoate

Certain bacterial species produce polymers of y-hydroxybutyric acid and other hydroxyalkanoic acids as storage polymers. These are biodegradable polymers with some desirable properties for manufacture of biodegradable packaging materials, and considerable effort is being devoted by ICI Ltd. and others to the development of bacterial fermentation processes to produce these polymers at a high molecular weight (66). 

A. Kaunzinger, P. Podebrad, R Liske, B. Maas, A. Dietiich and A. Mosandl, Stereochemical differentiation and simultaneous analysis of 3-,4- and 5-hydroxyalkanoic... 

Figure 15.7 Cliromatographic separation of cliiral hydroxy acids from Pseudomonas aeruginosa without (a) and with (h) co-injection of racemic standards. Peak identification is as follows 1, 3-hydroxy decanoic acid, methyl ester 2, 3-hydroxy dodecanoic acid, methyl ester 3, 2-hydroxy dodecanoic acid, methyl ester. Adapted from Journal of High Resolution Chromatography, 18, A. Kaunzinger et al., Stereo differentiation and simultaneous analysis of 2- and 3-hydroxyalkanoic acids from hiomemhranes hy multidimensional gas cliromatog-raphy , pp. 191 -193, 1995, with permission from Wiley-VCH. (continuedp. 419)...

Table 1. Methyl 2-Amino-3-hydroxyalkanoates by Addition of Azaenolatcs from 2.5-Dihydro-3.6-dimeth-oxypyrazines to Saturated Aldehydes and Ketones, Followed by Hydrolysis...

By simply hydrolyzing the easily accessible 2-hydroxy-2-methylalkanenitriles with concentrated acid, 2-hydroxy-2-methylalkanoic acids are obtained without measurable racemization (Table 3). The reaction sequence from the starting ketone to the carboxylic acid can be carried out in one pot without isolation of the cyanohydrin. The enantiomeric excesses of the (/ )-cyanohydrins and the (ft)-2-hydroxyalkanoic acids are determined from the ( + )-(/T)-Mosher ester derivatives and as methyl alkanoates by capillary GC, respectively. The most efficient catalysis by (R)-oxynitrilase is observed for the reaction of hydrocyanic acid with 2-alkanoncs. 3-Alkanoncs are also substrates for (ft)-oxynitrilase, to give the corresponding (/ )-cyanohydrins32. 

Poly(hydroxyalkanoic acid)s BiopoF Monsanto Environmental Biosynthesis by bacteria or transgenic plants... 

Finally, the synthesis of biodegradable poly(hydroxyalkanoic acids) (PHA) by bacteria or genetically modified plants should be mentioned. The microbiology, biochemistry, and genetics of PHA biosynthesis have been reviewed by several authors52,105,405 407 and are beyond the scope of this chapter. 

PHA degradation, 43 PHAs. See Poly(hydroxyalkanoic acid)s (PHAs)... 

Poly(hydroxyalkanoic acid)s (PHAs), 27, 31, 41-43 biodegradable, 90 Poly(4-hydroxybenzoic acid) (PHBA), 49-50... 

Takagi, Y., Yasuda, R., Yamaoka, M. and Yamane, T. 2004. Morphologies and mechanical properties of polylactide blends with medium chain length poly(3-hydroxyalkanoate) and chemically modified poly(3-hydroxyalkanoate). Journal of Applied Polymer Science 93 2363-2369. 

Formation of Polyesters by Pseudomonas oleovorans Effect of Substrates on Formation and Composition of Poly-(R)-3-Hydroxyalkanoates and Poly-(R)-3-Hydroxyalkenoates. Applied Environmental and Microbiology, 54, 2924-2932. 

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. 

Keywords. Bacterial polyester, Medium-chain-length poly(3-hydroxyalkanoates), Pseudomonas oleovorans, Pseudomonas putida, Functional poly(3-hydroxyalkanoates), Short-chain-length poly(3-hydroxyalkanoates)... 

Short-Chain-Length Poly(3-hydroxyalkanoates) [poly(HASCL)s]. . 56... 

Medium-Chain-Length-PHAs Containing Substituted 3-Hydroxyalkanoates... 

Many bacteria are able to synthesize polyesters of hydroxyalkanoic acids and to accumulate these water insoluble polyhydroxyalkanoic acids (PHA) in the cytoplasm as inclusions and as storage compounds for energy and carbon these in-... 

PHA synthases are the key enzymes of PHA biosynthesis. These enzymes catalyze the covalent linkage between the hydroxyl group of one and the carboxyl group of another hydroxyalkanoic acid. The substrates of PHA synthases are the coenzyme A thioesters of hydroxyalkanoic acids there is no evidence that PHA synthases can utilize either free hydroxyalkanoic acids or other derivatives of hydroxyalkanoic acids. With respect to size, structure, and substrate specificity, three different types of PHA synthases (I, II, and III) can be distinguished (see below). 

The polymerase is stereospecific. It accepts only the D-(-)-stereoisomer which is generally formed by the NADPH-linked reductase. With respect to chain length of the activated fatty acids the specificity of the polymerase varies in different organisms. It links not only C4 3-acyl moieties but also C5 compounds when forming the polyester molecule [26]. It also polymerizes 3-hy-droxy-, 4-hydroxy-, and 5-hydroxyalkanoates from C3 to C5 monomers, but not C6 or higher (e.g., in R. eutropha) [27-31]. In pseudomonads, in contrast, it links C6 to C14 3-hydroxyalkanoyl-CoA [32]. 

Fig. 2A-F. Hydroxy acid monomers of PHAs with varied polymer backbones A standard 3-hydroxyalkanoic acid monomer B 2-methyl-3-hydroxyalkanoic acid monomer C 2,2-di-methyl-3-hydroxyalkanoic acid monomer D 4-hydroxyalkanoic acid monomer E 5-hydroxy-alkanoic acid monomer F 6-hydroxyalkanoic acid monomer. (R indicates alkyl residue or H)...

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