초록 |
Combinatorial biosynthesis can be defined as modifying biosynthetic pathways generally by combining the natural or engineered biosynthetic enzyme activities from disparate sources and exploiting substrate promiscuity of biosynthetic machinery to produce “unnatural” natural products with altered structures with aims to expand the structural diversity of natural products and improve their pharmaceutical properties. In the broad sense, combinatorial biosynthesis would encompass precursor-directed biosynthesis, which incorporates chemically synthesized precursor in vivo into a natural products by the endogenous natural biosynthetic catalysts using their inherent substrate promiscuity, and mutasynthesis, where the gene producing the natural substrates is disrupted thus more efficiently incorporating the modified precursors. Some recent examples for combinatorial biosynthesis of approaches to create the structural diversity of natural products including polyketides and aminoglycosides will be presented. |