Metabolic engineering and pathway construction for biotechnological production of relevant polyhydroxyalkanoates in microorganisms

Prokaryotes synthesize a wide range of different polyhydroxyalkanoic acids (PHA) and accumulate these polyesters as insoluble inclusions in the cytoplasm for storage of carbon and energy. PHAs are considered for various technical applications due to interesting physical and material properties. In order to establish economically feasible biotechnological production systems and to obtain PHAs from cheap carbon sources with a preference from renewable resources, CO2 or residual materials, efforts are undertaken to engineer novel pathways in recombinant prokaryotic and eukaryotic organisms. This requires transfer of a PHA synthase structural gene, expression of an enzymatically active PHA synthase protein and in particular engineering of pathways that provide this key enzyme of PHA synthesis with suitable substrates at sufficient concentrations. Only if all three aspects are well considered, a functional active PHA biosynthesis pathway will be expressed allowing PHA biosynthesis from central intermediates and therefore biotechnological production from renewable carbon sources or even CO2. This review will focus on the engineering of pathways resulting in the formation of PHAs containing 3-hydroxyvaleric acid, medium-chain-length 3-hydroxyalkanoic acids or 4-hydroxybutyric acid as constituents. (C) 2003 Elsevier Science B.V. All rights reserved.