Metabolic Engineering: New Approaches in Pharmaceutical Production

Abstract

Natural products, natural products-derived, and natural products-inspired compounds represent a major sector of drugs and drug leads. Nature has the potential to produce compounds built to interact with biological systems. Mostly are produced as secondary metabolites by a living organism for different purposes such as defense and communication. Natural compounds usually contain multiple chiral centers within strictly specific molecular architecture that are very difficult to be obtained by combinatorial synthesis for economic supply of drugs. Meanwhile, natural compounds serving as drugs or precursors for synthesis are having several drawbacks with insufficient and fluctuating supply as the most serious problems. For these reasons metabolic engineering exploiting advanced biotechnology techniques such as sequencing, recombinant DNA, and protein engineering can add new incentives to produce secondary metabolites. Metabolic engineering is based on manipulating metabolic networks/pathways within prokaryotic organisms or cultured eukaryotes. Both organisms have common features, including a cytoplasmic membrane, DNA that codes for genetic information, and RNA that is subsequently translated into proteins. Successful study of the biosynthetic pathways responsible for the production of natural products together with advances in fermentation technologies and expression systems, variation in tool kits, and mutation tools allowed metabolic engineering to be a promising approach for the targeted production of a wide variety of natural compounds (taxol, camptothecin, vincristine, artemisinin, silymarin) with bacterial, fungal, and plant origins.