HYDROXYHEXANOATE COPOLYMER

Barham PJ, Keller A (1986) The relationship between microstructure and mode of fracture in polyhydroxybutyrate. J Polym Sd Polym Phys Ed 24 69-77 Bond EB (2003) Fiber spinning behavior of a 3-hydorxybutyrate/3-hydroxyhexanoate copolymer. Macromol Symp 197 19-31... 

Details are given of the biocompatibility of hydroxybutyrate-hydroxyhexanoate copolymer with bone marrow stromal cells in vitro. The adsorption of fibronectin on the material was studied by enzyme-linked immunosorbent assay. The wettability and thermal properties of copolymer films were also studied by contact angle goniometer, TGAand DSC. Potential applications in bone tissue engineering are mentioned. 37 refs. 

Garcfa-Garcfa JM, Quijada-Garrido I, Ldpez L, Paris R, Nunez-Ldpez MT, de la Pena Zarzuelo E, Garrido L. The surface modification of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) copolymers to improve the attachment of urothelial cells. Mater Sci Eng C 2013 33 362-369. 

There is considerable interest in synthesizing copolymers. This is actually possible if organisms are confronted with mixtures of so-called related and unrelated substrates. Copolymers can also be synthesized from unrelated substrates, e.g., from glucose and gluconate. The 3-hydroxydecanoate involved in the polyester is formed by diversion of intermediates from de novo fatty-acid synthesis [41,42]. Related , in this context, refers to substrates for which the monomer in the polymer is always of equal carbon chain length to that of the substrate offered. Starting from related substrates, the synthesis pathway is closely connected to the fatty-acid /1-oxidation cycle [43]. In Pseudomonas oleovor-ans, for example, cultivated on octane, octanol, or octanoic acid, the synthesized medium chain length polyester consists of a major fraction of 3-hydroxyoc-tanoic acid and a minor fraction of 3-hydroxyhexanoic acid. If P. oleovorans is cultivated on nonane, nonanol, or nonanoic acid, the accumulated polyester comprises mainly of 3-hydroxynonanoate [44]. 

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]. 

Many other polymers of this class are produced by a variety of organisms these include poly-4-hydroxybutyrate (P4HB), polyhydroxyvalerate (PHV), poly-hydroxyhexanoate (PHH), polyhydroxyoctanoate (PHO) and their copolymers. 

Procter Gamble is the other leading pioneer on the field of PHA biodegradable polymers. The Nodax biopolymers are based on the copolymer PHBH, a copolymer polyester of 3-hydroxybutyric and 3-hydroxyhexanoic acid. The higher the 3-hydroxyhexanoic acid comonomer component, the more flexible... 

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... 

Figure 8 shows the amount of 3-(2-hydroxyethoxy)-propanoic acid (HPA) and 6-hydroxyhexanoic acid (HHA) migrating from the CL/DXO copolymers as a function of copolymer composition and hydrolysis time. Figure 8a shows that the amount of HPA released from the materials increased both as a function of hydrolysis time and as the DXO-content in the copolymer increased. In the case of HHA release the situation was more complicated and the largest amount of HHA was released from the copolymers with intermediate CL-contents (Fig. 8b). In relation to the CL- content, the largest amount of HHA was released from the DXO-rich copolymers (Fig. 8c). This was explained by the faster hydrolysis rate of DXO-units, which also enhances the release of HHA.

Fig. 9 The relative amount of 6-hydroxyhexanoic acid (HHA) and 3-(2-hydroxyethoxy)-propanoic acid (HPA) formed during hydrolysis of a DXO/CL/DXO triblock copolymer, b CL/DXO multiblock copolymer, c Random crosslinked CL/DXO copolymer and d PCL homopolymer. All of the copolymers had 60 mol % CL imits and 40 mol % DXO imits. The polymers were hydrolyzed for different times in phosphate buffer pH 7.4 and 37 °C. After the predetermined hydrolysis times the monomeric degradation products were extracted by solid-phase extraction and analyzed by GC-MS. Reprinted from [160] with permission of American Chemical Society. American Chemical Society (2007)...

PHB-co-PHV [54] is obtained from Azotobacter chroococcum [58, 63). The biodegradation is slower for the copolymers than poly-3-hydroxybutyrate. 3-hydroxy-n-phenylalkanoic acids and 3-hydroxyaliphatic acids are obtained from Pseudomonas putida [59]. Poly (3-hydroxyoctanoic acid) and poly (6-hydroxyhexanoic acid) and poly (3-hydroxyoctanoic acid) [64], Poly-(R)-3-hydroxybutyrate/polyphosphate (PHB/polyP) complexes are isolated from the plasma membranes of bacteria [65,66]. Polyhydroxyoctanoate is produced by feeding octanoic acid to Pseudomonas oleovorans [67]. 

The nomenclature of PHAs and their classification are still in the process of evolving, because new structures are continuing to be discovered. The main biopolymer in the PHA family is a homopolymer polyhydroxybutyrate (PHB). The most conunon copolymer is poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV), whose chemical structure is presented in Figure 9.4. However, there are others, such as poly(hydroxybulyrate-co-hydroxyhexanoate) (PHBHx), poly(hydroxybutyrate-co-hydroxyoctanoate) (PHBO) and poly(ltydroxybulyrate-co-hydroxyoctadecanoate) (PHBOd), for example. 

Another terpolymer poly(3-hydroxybutyrate-co-4-hydroxybutyrate-co-3-hydroxyhexanoate) [P(3HB-co-4HB-co-3HHx)] was found to have better thermal stability due to the introduction of 4HB and 3HHx monomers into P(3HB) (Xie and Chen 2008). It has lower crystalUnity and better flexibility compared to P(3HB) homopolymer and copolymers. Poly(3-hydroxybutyrate-C( -3-hydroxyvalerate-co-4-hydroxybutyrate) [P(3HB-co-3HV-co-4HB)] also showed superior properties over those of 3HB and its copolymer (Madden et al. 2000 Chanprateep and Kulpreecha 2006). Table 2.3 shows the comparison of different types of PHA polymer. 

Several types of bacterial polyesters that are produced by biosynthesis are poly-3-hydroxybutyrate, poly-4-hydroxybutyrate, poly-3-hydroxyvalerate, poly-3-hydroxyhexanoate, poly-3-hydroxy-heptanoate, etc., and their respective copolymer combinations. Due to their ability to degrade naturally in variety of environments, they will find a lot of applications in disposal items, short-term packaging, and also considered biocompatible in contact with living tissues and can be used for biomedical applications (e.g., drug encapsulation, tissue engineering) (Chauhan, 2012). 

Metabolix and ADM have formed the joint venture Telles to produce and market polyhydroxyalkanoate (PHA) resins based on corn sugar. The Japanese company Kaneka has just recently announced to launch a 1000 mt production facility for the manufacture of Kaneka PHBH, a copolymer of 3-hydroxybutyrate and 3-hydroxyhexanoate [13]. 

Tiipathi, L., Wu, L.P., Chen, J. and Chen, G.Q. (2012) Synthesis of Diblock copolymer poly-3-hydroxybutyrate -block-poly-3-hydroxyhexanoate [PHB-b-PHHx] by a -oxidation weakened Pseudomonas putida KT2442. Microbial Cell Factories, 44,1-11. 

To date, various block copolymers have been produced using biological systems. This includes poly(3HB-fo-4HB) [17], P(3HB)-f>-poly(3-hydroxyvalerate-co-3-hydroxyheptanoate) [18], PHB-f -poly(hydroxyhexanoate) [19], poly 3HB-fc-poly(3-hydroxyheptanoate) [P(3HP)] [20], P(3HP)-f -poly(4-hydroxybutyrate) [P(4HB)] [21], poly(3-hydroxyhexanoate)-fe-poly(3-hydroxydecanoate)-co-[3-hydroxydodecanoate (3HDD)] [22] and poly[3-HDD-f -poly(3-hydroxy-9-decanoate)] [23]. These studies were motivated by the fact that although random copolymers, such as poly(3HB-co-3HV) and poly(3HB-co-4HB), exhibit useful mechanical and thermal properties they suffer from a deterioration of polymer properties due to the effect of ageing. It was found that all block copolymers exhibited improved properties compared with the two relative homopolymers, random and blend polymers. Various... 

The second PHA synthesis pathway (pathway II) is related to fatty acid uptake by microorganisms. After fatty acid P-oxidation, acyl-CoA enters the PHA monomer synthesis process. Enzymes including 3-ketoacyl-CoA reductase, epimerase, (I )-enoyI-CoA hydratase/enoyl-CoA hydratase I, acyl-CoA oxidase (putative), and enoyl-CoA hydratase I (putative) were found to be involved in supplying the PHA precursor 3-hydroxyacyl-CoA for PHA synthesis. Pseudomonas putida, Pesudomonas aeruginosa, and A. hydrophila are able to use pathway n to synthesize medium-chain-length (mcl) PHA or copolymers of (/ )-3-hydroxybutyrate (R3HB) and (R)-3-hydroxyhexanoate (PHBHHx). 

Abe H, Doi Y, Aoki H, Akehata T, Hori Y, Yamaguchi A (1995) Physical properties and enzymatic degradability of copolymers of (R)-3-hydroxybutyric and 6-hydroxyhexanoic acids. Macromolecules 28 7630-763... 

Fukui T, Doi Y (1998) Expression and characterization of (/f)-specdlic enoyl coenzyme A hydiatase involved in polyhydroxyalkanoate biosynthesis by Aeromonas caviae. J Bacteriol 180 667-673 Fukui T, Abe H, Doi Y (2002) Engineering of Ralstonia euttopha for production of poly(3-hydroxy-butyrate-co-3-hydroxyhexanoate) from fructose and solid-state properties of the copolymer. Biomacromolecules 3 618-624... 

Taking into account the advantages and the limitations of both kind of polymers, different approaches based on biochentical, genetic and bioprocess innovation have attempted to obtain hybrid scl-mcl copolymers scl C -CJC copolymers, poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate]/poly[(/ )-3-hydroxybu-tyrate-co-(R)-3-hydroxyhexanoate Fig. 2 to generate new PHAs with different or improved physiochemical properties and broader biotechnological applications (Lee et al. 2000b Lu et al. 2004 Ramsay et al. 1990 Hanggi 1995 Lenz and Marchessault 2005 Wei et al. 2009). 

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