title: Methylation-dependent acyl transfer between polyketide synthase and nonribosomal peptide synthetase modules in fungal natural product biosynthesis.
abstract: Biochemical studies of purified and dissected fungal polyketide synthase and nonribosomal peptide synthetase (PKS-NRPS) hybrid enzymes involved in biosynthesis of pseurotin and aspyridone indicate that one α-methylation step during polyketide synthesis is a prerequisite and a key checkpoint for chain transfer between PKS and NRPS modules. In the absence of the resulting γ-methyl feature, the completed polyketide intermediate is offloaded as an α-pyrone instead of being aminoacylated by the NRPS domain. These examples illustrate that precisely timed tailoring domain activities play critical roles in the overall programming of the iterative PKS (and NRPS) functions.
authors.affiliation: Department of Chemical and Biomolecular Engineering and ‡Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zou
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tsunematsu
authors.forename: Mancheng
authors.initials: M
authors.lastname: Tang
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000595:Amino Acid Sequence; D001669:Biochemical Phenomena; D001685:Biological Factors / Q000096:biosynthesis* / Q000737:chemistry; D005658:Fungi / Q000737:chemistry* / Q000378:metabolism*; D008745:Methylation; D015394:Molecular Structure; D010453:Peptide Synthases / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D048630:Polyketide Synthases / Q000737:chemistry* / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods; D011753:Pyrones / Q000737:chemistry*; D011760:Pyrrolidinones / Q000378:metabolism
chemical_list: D001685:Biological Factors; D011753:Pyrones; D011760:Pyrrolidinones; C012013:pseurotin; D048630:Polyketide Synthases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase