title: Polyketide Ring Expansion Mediated by a Thioesterase, Chain Elongation and Cyclization Domain, in Azinomycin Biosynthesis: Characterization of AziB and AziG.
abstract: The azinomycins are a family of potent antitumor agents with the ability to form interstrand cross-links with DNA. This study reports on the unusual biosynthetic formation of the 5-methyl naphthoate moiety, which is essential for effective DNA association. While sequence analysis predicts that the polyketide synthase (AziB) catalyzes the formation of this naphthoate, 2-methylbenzoic acid, a truncated single-ring product, is formed instead. We demonstrate that the thioesterase (AziG) acts as a chain elongation and cyclization (CEC) domain and is required for the additional two rounds of chain extension to form the expected product.
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Shogo
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Simkhada
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Huitu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
authors.forename: Megan S
authors.initials: MS
authors.lastname: Erb
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Howard
authors.initials: H
authors.lastname: Williams
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Fedoseyenko
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: William K
authors.initials: WK
authors.lastname: Russell
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Doyong
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Nathan
authors.initials: N
authors.lastname: Fleer
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Ealick
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Coran M H
authors.initials: CM
authors.lastname: Watanabe
mesh_terms: D000970:Antineoplastic Agents; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006020:Glycopeptides / Q000096:biosynthesis*; D048630:Polyketide Synthases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D006020:Glycopeptides; D048630:Polyketide Synthases