Microbial production of lactate-containing polyesters.
Bottom Line: Systems metabolic engineering integrating traditional metabolic engineering with systems biology, synthetic biology, protein/enzyme engineering through directed evolution and structural design, and evolutionary engineering, enabled microorganisms to efficiently produce natural and non-natural products.Here, we review the strategies for the metabolic engineering of microorganisms for the in vivo biosynthesis of lactate-containing polyesters and for the optimization of whole cell metabolism to efficiently produce lactate-containing polyesters.Also, major problems to be solved to further enhance the production of lactate-containing polyesters are discussed.
Affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Program), Center for Systems and Synthetic Biotechnology, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea; Institute for the BioCentury, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.Show MeSH
Mentions: In nature, many microorganisms accumulate PHAs as carbon, energy and redox storage materials when they encounter unfavourable growth condition in the presence of excess carbon source. To date, more than 150 different kinds of 3-, 4-, 5- and 6-hydroxycarboxylic acids (Fig. 2) have been identified as monomer constituents of PHAs that are synthesized and accumulated as distinct granules in the cytoplasm of microorganisms (Steinbuchel and Valentin, 1995). Together with several key enzymes for the synthesis of PHAs from hydroxyacyl-CoAs, the metabolic pathways including glycolysis, TCA cycle, fatty acid β-oxidation and fatty acid biosynthesis are involved (Fig. 3). The key steps for PHA biosynthesis are as follows: generation of hydroxyacyl-CoA (HA-CoA) and polymerization of HA-CoAs into PHA by PHA synthase. When hydroxycarboxylic acids are generated in the cells, CoA is transferred to the hydroxycarboxylic acids to yield HA-CoAs that are required for PHA biosynthesis. The PHA monomer spectrum is quite broad with respect to the carbon numbers (3–16), the degree of saturation, different functional groups attached and the position of hydroxyl group (Fig. 2) (Steinbuchel and Valentin, 1995). Furthermore, PHA monomers are all in (R)-configuration, if a chiral centre exists on the carbon the hydroxyl group is attached to (Lee, 1996; Madison and Huisman, 1999). The material characteristics of PHAs are governed by the monomer constituents, and thus can be largely designed by metabolic engineering. However, among the various HA-CoAs synthesized in the host strain, only HA-CoAs that fit in the active site of PHA synthase can be incorporated to form PHAs.
Affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Program), Center for Systems and Synthetic Biotechnology, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea; Institute for the BioCentury, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.