Page 84 - Biodegradable Polyesters

62 3 Microbial Synthesis of Biodegradable Polyesters: Processes, Products, Applications

as shell–core particles with a hydrophobic polyester core surrounded by
phospholipids and specific proteins constituting the shell.
There are a variety of metabolic tools at our disposal to control the polyester
composition and the material properties of the bionanoparticle core. Recently,
more knowledge about the topology of particle surface-attached proteins as well
as the biogenesis, that is, the molecular mechanism of self-assembly of polyester
particles has been gained. The fusion of a functional protein (GFP) to different
polyester synthase has been published recently, which did not affect bionanopar-
ticle formation inside the bacterial cell [55]. The GFP was displayed at the particle
surface. It has been shown that the size of the particles is dependent on attached
proteins and the cell division machinery. Particle sizes with an average diameter
ranging from 50 to 500 nm have been already obtained. To summarize, the core
composition, the surface functionality, and the size of these bionanoparticles can
be highly controlled and harnessed by a biotechnological production process.
The design of the nanoparticles should be achievable by in vivo biosynthesis
of polyester particles in recombinant E. coli (controlling the expression of genes,
which encode particle biosynthesis/biogenesis-relevant proteins and genes, which
encode fusion proteins of the aforementioned proteins) as well as in vitro, using
purified enzymes/proteins and/or the respective fusion proteins relevant for
polyester particle biogenesis. There is potential for more design space by further
processing of the isolated particles with respect to replacement of non-covalently
surface-attached biomolecules with surfactants, phospholipids, or proteins as
well as by affinity purification [20] and in diagnostics using bioparticle display of
functional eukaryotic proteins in combination with fluorescence-activated cell
sorting [66]. Patents have been filed considering the use of biopolyester particles
encapsulating a drug during in vitro formation and for the general ex vivo use of
biotechnologically produced functionalized biopolyester particles. This suggests
a commercial potential of these naturally occurring nanostructures’ covalent
cross-linking of biomolecules to the particle surface. Nanoparticles with surface
areas constituting 1–100% of protein (engineered protein) or 0–99% of phos-
pholipids, or other relevant amphipathic molecules could be generated. There
is commercial interest in exploiting the unique potential of designed biogenic
polyester particles suitable for, for example, protein production, bioseparation,
drug delivery, and vaccine design.
3.8.6
Future Development of PHA-Based Industry

To help the commercial applications of PHAs, two aspects should be considered.
The first one is to lower the production costs of PHA and the second is to find
high value added applications of PHAs. Much effort has been directed to these
two aspects, besides the basic research

3.8.6.1 The Development of Low-Cost PHA Production Technology
To lower PHA production costs, genetic engineering technology, pathway mod-
ification, or even synthetic biology approaches should be taken to develop super