title: Biosynthetic engineering of natural products for lead optimization and development.
abstract: It is now possible to rapidly and rationally modify, at a genetic level, the machinery responsible for natural product biosynthesis. This provides the opportunity to design new structures and to optimize natural product lead compounds in a way that would be extremely difficult through synthetic chemistry means alone. The technology can also be used to overcome limitations of compound supply, which might otherwise preclude natural products from progressing into clinical trials. Described herein are some recent examples which highlight how biosynthetic engineering has been applied to drug discovery and development, and which attempt, in particular, to demonstrate how the technology functions most effectively when combined with synthetic organic and medicinal chemistry.
authors.affiliation: Biotica Technology Ltd, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, UK. barrie.wilkinson@biotica.com
authors.forename: Barrie
authors.initials: B
authors.lastname: Wilkinson
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Moss
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D001419:Bacteria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D001688:Biological Products / Q000096:biosynthesis*; D001709:Biotechnology / Q000379:methods; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D005818:Genetic Engineering; D009154:Mutation
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D001688:Biological Products