title: Harnessing natural product assembly lines: structure, promiscuity, and engineering.
abstract: Many therapeutically relevant natural products are biosynthesized by the action of giant mega-enzyme assembly lines. By leveraging the specificity, promiscuity, and modularity of assembly lines, a variety of strategies has been developed that enables the biosynthesis of modified natural products. This review briefly summarizes recent structural advances related to natural product assembly lines, discusses chemical approaches to probing assembly line structures in the absence of traditional biophysical data, and surveys efforts that harness the inherent or engineered promiscuity of assembly lines for the synthesis of non-natural polyketides and non-ribosomal peptide analogues.
authors.affiliation: Department of Chemistry, NC State University, Raleigh, NC, 27695-8204, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Ladner
authors.affiliation: Department of Chemistry, NC State University, Raleigh, NC, 27695-8204, USA. gjwillia@ncsu.edu.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Williams
mesh_terms: D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000235:genetics; D060847:Metabolic Engineering; D010455:Peptides / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism
chemical_list: D001688:Biological Products; D010455:Peptides; D061065:Polyketides
keywords: Combinatorial biosynthesis; Enzyme engineering; Non-ribosomal peptide synthases; Polyketide synthases; Synthetic biology