title: Unusual activities of the thioesterase domain for the biosynthesis of the polycyclic tetramate macrolactam HSAF in Lysobacter enzymogenes C3.
abstract: HSAF is an antifungal natural product with a new mode of action. A rare bacterial iterative PKS-NRPS assembles the HSAF skeleton. The biochemical characterization of the NRPS revealed that the thioesterase (TE) domain possesses the activities of both a protease and a peptide ligase. Active site mutagenesis, circular dichroism spectra, and homology modeling of the TE structure suggested that the TE may possess uncommon features that may lead to the unusual activities. The iterative PKS-NRPS is found in all polycyclic tetramate macrolactam gene clusters, and the unusual activities of the TE may be common to this type of hybrid PKS-NRPS.
authors.affiliation: Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588, United States.
authors.forename: Lili
authors.initials: L
authors.lastname: Lou
authors.forename: Haotong
authors.initials: H
authors.lastname: Chen
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Cerny
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Li
authors.forename: Yuemao
authors.initials: Y
authors.lastname: Shen
authors.forename: Liangcheng
authors.initials: L
authors.lastname: Du
mesh_terms: D000577:Amides / Q000737:chemistry / Q000378:metabolism; D000935:Antifungal Agents / Q000138:chemical synthesis; D047029:Lactams, Macrocyclic / Q000138:chemical synthesis*; D053528:Lysobacter / Q000201:enzymology*; D005810:Multigene Family; D048630:Polyketide Synthases / Q000096:biosynthesis*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013869:Thiolester Hydrolases / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000577:Amides; D000935:Antifungal Agents; C557945:HSAF compound; D047029:Lactams, Macrocyclic; D048630:Polyketide Synthases; D013869:Thiolester Hydrolases