Page 86 - Biodegradable Polyesters

64 3 Microbial Synthesis of Biodegradable Polyesters: Processes, Products, Applications

3.8.6.3 High Value Added Applications
With the wide variety of applications of PHA, medical applications of PHA seem
to be the most economically practical area. It is vital to exploit and develop the
application of PHAs in the medical field. Most of the PHAs available in sufficient
quantities, including PHB, PHBV, PHBHHx, P4HB, P3HB4HB, and PHO, have
been studied for bio-implant applications. All of them showed good biocompati-
bility and some biodegradability. Of these, P4HB has been approved by the FDA
®
for suture application with the trade name TephaFLEX marketed by Tepha Inc.,
of Cambridge, Mass., USA. Future efforts have been directed to develop more
medical applications for PHA, mostly, three-dimensional scaffolds for implant
purposes.

3.8.6.4 Other Future Applications
PHA operons expressed in prokaryotes or eukaryotes can be used to help enhance
cellular robustness. This mechanism should be tested in more industrial microbial
strains aiming to select strains with better resistance to the stressed conditions
and, as such, enhanced yields of the bio-products, including antibiotics, vitamins,
and amino acids.
The amphiphilic proteins on PHA granule surfaces should be exploited for more
applications in specific drug targeting, cell sorting, protein purification, and so on.

3.8.6.5 Microbial Synthesis of Poly(lactic acid) (PLA)
There was a breakthrough when it was found that one mutant of PHA synthase
was capable of incorporating lactic acid (LA) from its CoA form, lactyl-CoA
(LA-CoA), into the polymer chain [67]. PHAs containing 2HA monomers, lactic
acid (LA), glycolate (GL), and 2HB can be synthesized by engineered microbes
in which the broad substrate specificities of PHA synthase and propionyl-CoA
transferase (PCT) are critical factors for the incorporation of the monomers
into the polymer chain. LA-based polymers, such as P[LA-co-3HB], have the
properties of pliability and stretchiness which are distinctly different from those
of the rigid poly(lactic acid) and P(3HB) homopolymers.
To obtain a new 2HA-polymerizing PHA synthase, the class I PHA synthase
from R. eutropha was engineered so as to achieve the first incorporation of LA
units. The analysis of the polymer synthesized using this new LA-polymerizing
PHA synthase unexpectedly focused on the studies on block copolymer biosyn-
thesis.
From the point when LA polymerization was first demonstrated, the common
question has been whether it is possible to produce PLA homopolymer. The
answer has been “no” because recombinant E. coli expressing only a combination
of PhaC1PsSTQK and PCT did not produce any polymer [67]. The supply of
3HB-CoA seemed to be essential to the production of LA-incorporated poly-
mers, which was a serious obstacle for the biosynthesis of PLA and/or PLA-like
polymers.
In 2011, the production of LA-incorporated polymer with 96 mol% LA was
achieved through chance. Similar results were obtained with valeric acid added