Systems biological approach for the production of various polyhydroxyalkanoates by metabolically engineered Escherichia coli

Abstract

Metabolic engineering strategies have been developed based on ever increasing molecular and genetic information of polyhydroxyalkanoate (PHA) biosynthesis in natural PHA producing bacteria, and used for developing recombinant Escherichia coli strains with enhanced PHA biosynthesis activity. Recently, systems level metabolic engineering approaches based on genomics, proteomics and fluxomics have been taken in designing an optimal bioprocess for the production of various PHAs in recombinant E. coli. For examples, in silico metabolic flux analysis (MFA) and proteome analysis revealed that several central metabolic enzymes including Eda, Fba and TpiA were amplified during poly(3-hydroxybutyrate)[P(3HB)] biosynthesis to support more acetyl-CoA and NADPH. Also, a genome informatics approach was successfully taken to identify various FadB homologous enzymes including YfcX, YdbU, PaaF and PaaG, and a new enoyl-CoA hydratase MaoC, which are involved in PHA biosynthesis from fatty acid in fadB mutant E. coli strains. These new systems level findings were employed to design metabolically engineered E. coli strains for the enhanced production of PHAs and production of novel PHAs. Therefore, systems biological approach is a robust way to improve the metabolic activities of recombinant E. coli locally as well as globally for the enhanced production of PHAs.