title: Characterization of the Ketosynthase and Acyl Carrier Protein Domains at the LnmI Nonribosomal Peptide Synthetase-Polyketide Synthase Interface for Leinamycin Biosynthesis.
abstract: Leinamycin (LNM) is biosynthesized by a hybrid nonribosomal peptide synthetase (NRPS)-acyltransferase (AT)-less type I polyketide synthase (PKS). Characterization of LnmI revealed ketosynthase (KS)-acyl carrier protein (ACP)-KS domains at the NRPS-PKS interface. Inactivation of the KS domain or ACP domain in vivo abolished LNM production, and the ACP domain can be phosphopantetheinylated in vitro. The LnmI KS-ACP-KS architecture represents a new mechanism for functional crosstalk between NRPS and AT-less type I PKS in the biosynthesis of hybrid peptide-polyketide natural products.
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin , Madison, Wisconsin 53705, United States.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin , Madison, Wisconsin 53705, United States.
authors.forename: Gong-Li
authors.initials: GL
authors.lastname: Tang
authors.forename: Guohui
authors.initials: G
authors.lastname: Pan
authors.forename: Chin-Yuan
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin , Madison, Wisconsin 53705, United States.
authors.forename: Ben
authors.initials: B
authors.lastname: Shen
mesh_terms: D000213:Acyl Carrier Protein / Q000737:chemistry / Q000378:metabolism*; D007769:Lactams / Q000737:chemistry / Q000378:metabolism*; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism*; D008968:Molecular Conformation; D010453:Peptide Synthases / Q000737:chemistry / Q000378:metabolism*; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism*; D000072417:Protein Domains; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism*; D013871:Thiones / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000213:Acyl Carrier Protein; D007769:Lactams; D018942:Macrolides; D013844:Thiazoles; D013871:Thiones; C059000:leinamycin; D048630:Polyketide Synthases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase