Metabolic engineering of microorganisms: general strategies and drug production.

Many drugs and drug precursors found in natural organisms are rather difficult to synthesize chemically and to extract in large amounts. Metabolic engineering is playing an increasingly important role in the production of these drugs and drug precursors. This is typically achieved by establishing new metabolic pathways leading to the product formation, and enforcing or removing the existing metabolic pathways toward enhanced product formation. Recent advances in system biology and synthetic biology are allowing us to perform metabolic engineering at the whole cell level, thus enabling optimal design of a microorganism for the efficient production of drugs and drug precursors. In this review, we describe the general strategies for the metabolic engineering of microorganisms for the production of drugs and drug precursors. As successful examples of metabolic engineering, the approaches taken toward strain development for the production of artemisinin, an antimalarial drug, and benzylisoquinoline alkaloids, a family of antibacterial and anticancer drugs, are described in detail. Also, systems metabolic engineering of Escherichia coli for the production of L-valine, an important drug precursor, is showcased as an important strategy of future metabolic engineering effort.