Towards Systems Metabolic Engineering of PHA Producers

Polyhydroxyalkanoates (PHAs) are natural polyesters that accumulate in numerous microorganisms as a carbon- and energy-storage material under the nutrient-limiting condition in the presence of an excess carbon source. PHAs are considered to be one of the potential alternatives to petrochemically derived plastics owing to their versatile material properties. Over the past few decades, extensive detailed biochemical, molecular-biological, and metabolic studies related to PHA biosynthesis have been carried out. Advances in our knowledge of PHA biosynthesis led to the development of engineered strains and fermentation processes for the production of PHAs with high efficiency. Even though the traditional metabolic engineering based on our rational thinking and trial-and-error type approaches allowed development of improved strains, further enhancement in the performance is expected through systems metabolic engineering, which is metabolic engineering integrated with systems-biological approaches. In this chapter, the strategies taken for the metabolic engineering of PHA producers are briefly reviewed. Then, genomic and proteomic studies performed to understand the PHA biosynthesis in the context of whole cell metabolism as well as to develop further engineered strains are reviewed. Finally, the strategies for the systems metabolic engineering of PHA producers are suggested; these will make it possible to produce PHAs with higher efficiencies and to develop tailor-made PHAs by systems-level optimization of the metabolic network and establishment of novel pathways.