Metabolic engineering of poly(3-hydroxyalkanoates): From DNA to plastic

Poly(3-hydroxyalkanoates) (PHAs) are a class of microbially produced polyes ters that have potential applications as conventional plastics, specificall y thermoplastic elastomers. A wealth of biological diversity in PHA formati on exists, with at least 100 different PHA constituents and at least five d ifferent dedicated PHA biosynthetic pathways. This diversity, in combinatio n with classical microbial physiology and modern molecular biology, has now opened up this area for genetic and metabolic engineering to develop optim al PHA-producing organisms. Commercial processes for PHA production were in itially developed by W. R. Grace in the 1960s and later developed by Imperi al Chemical Industries, Ltd., in the United Kingdom in the 1970s and 1980s. Since the early 1990s, Metabolix Inc. and Monsanto have been the driving f orces behind the commercial exploitation of PHA polymers in the United Stat es. The gram-negative bacterium Ralstonia eutropha, formerly known as Alcal igenes eutrophus, has generally been used as the production organism of cho ice, and intracellular accumulation of PHA of over 90% of the cell dry weig ht have been reported. The advent of molecular biological techniques and a developing environmental awareness initiated a renewed scientific interest in PHAs, and the biosynthetic machinery far PHA metabolism has been studied in great detail over the last two decades. Because the structure and monom eric composition of PHRs determine the applications for each type of polyme r, a variety of polymers have been synthesized by cofeeding of various subs trates or by metabolic engineering of the production organism. Classical mi crobiology and modem molecular bacterial physiology have been brought toget her to decipher the intricacies of PHA metabolism both for production purpo ses and for the unraveling of the natural role of PHAs. This review provide s an overview of the different PHA biosynthetic systems and their genetic b ackground followed by a detailed summation of how this natural diversity is being used to develop commercially attractive, recombinant processes for t he large-scale production of PHAs.