title: Bioengineering natural product biosynthetic pathways for therapeutic applications.
abstract: With the advent of next-generation DNA sequencing technologies, the number of microbial genome sequences has increased dramatically, revealing a vast array of new biosynthetic gene clusters. Genomics data provide a tremendous opportunity to discover new natural products, and also to guide the bioengineering of new and existing natural product scaffolds for therapeutic applications. Notably, it is apparent that the vast majority of biosynthetic gene clusters are either silent or produce very low quantities of the corresponding natural products. It is imperative therefore to devise methods for activating unproductive biosynthetic pathways to provide the quantities of natural products needed for further development. Moreover, on the basis of our expanding mechanistic and structural knowledge of biosynthetic assembly-line enzymes, new strategies for re-programming biosynthetic pathways have emerged, resulting in focused libraries of modified products with potentially improved biological properties. In this review we will focus on the latest bioengineering approaches that have been utilised to optimise yields and increase the structural diversity of natural product scaffolds for future clinical applications.
authors.affiliation: School of Chemistry and Manchester Interdisciplinary Biocentre, The University of Manchester, Manchester M1 7DN, UK.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Wu
authors.forename: Brian
authors.initials: B
authors.lastname: Law
authors.forename: Barrie
authors.initials: B
authors.lastname: Wilkinson
authors.forename: Jason
authors.initials: J
authors.lastname: Micklefield
mesh_terms: D057005:Bioengineering; D001688:Biological Products / Q000378:metabolism* / Q000627:therapeutic use*; D053898:Biosynthetic Pathways / Q000235:genetics*; D023281:Genomics; D006801:Humans; D005810:Multigene Family / Q000235:genetics; D015202:Protein Engineering
chemical_list: D001688:Biological Products