Biogenesis of microbial polyhydroxyalkanoate granules: a platform technology for the production of tailor-made...

Biopolyester (PHAs = polyhydroxyalkanoates) composed of hydroxy fatty acids represent a rather complex class of storage polymers synthesized by various eubacteria and archaea and are deposited as water-insoluble cytoplasmic nano-sized inclusions. These spherical shell-core particles are composed of a polyester core surrounded by phospholipids and proteins. The key enzymes of polyester biosynthesis and polyester particle formation are the polyester synthases, which catalyze the enantio-selective polymerization of (R)-hydroxyacyl-CoA thioesters to polyesters. Various metabolic routes have been identified and established in bacteria to provide substrate for polyester synthases. The role of the polyester synthases in morphogenesis and presumably self-assembly of these natural polyester particles will be described. Although not essential for particle formation, non-covalently attached proteins, the so-called phasins, can be found at the particle surface and are considered as structural proteins. A multiple alignment of 88 polyester synthases indicated an identity varying from 8% to 96% with eight strictly conserved amino acid residues. Protein engineering of polyester synthases and phasins was used to functionalize the polyester particle surface. The current knowledge enables the microbial and biocatalytic production of particles with controlled size, polyester core composition and surface functionality, which suggested numerous potential applications of these biocompatible and biodegradable nanostructures particularly in the medical field.