title: Identification of NanE as the thioesterase for polyether chain release in nanchangmycin biosynthesis.
abstract: The polyketide synthase (PKS) for the biosynthesis of the polyether nanchangmycin lacks an apparent thioesterase comparable to the type I thioesterase domains of the modular PKSs responsible for macrolide biosynthesis. Three candidate polyether chain-releasing factors were examined. Both the putative CR domain and the NanE protein appeared to be genetically relevant. Among the three heterologously expressed soluble proteins (recombinant CR domain, the ACP-CR didomain, and NanE) tested, only NanE hydrolyzed the polyether-SNAC. By contrast, recombinant DEBS TE from the erythromycin pathway, and the recombinant MonAX, a type II TE associated with the polyether monensin biosynthesis for which a homolog has not been detected in the nanchangmycin cluster, hydrolyzed a diketide-SNAC but not the polyether-SNAC. We could thus conclude that NanE is a dedicated thioesterase mediating the specific release of the polyether chain during nanchangmycin biosynthesis.
authors.affiliation: Laboratory of Microbial Metabolism and School of Life Science & Biotechnology, Shanghai Jiaotong University, Shanghai 200030, China.
authors.forename: Tiangang
authors.initials: T
authors.lastname: Liu
authors.forename: Delin
authors.initials: D
authors.lastname: You
authors.forename: Chiara
authors.initials: C
authors.lastname: Valenzano
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Sun
authors.forename: Jialiang
authors.initials: J
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zhou
authors.forename: David E
authors.initials: DE
authors.lastname: Cane
authors.forename: Zixin
authors.initials: Z
authors.lastname: Deng
mesh_terms: D000595:Amino Acid Sequence; D002853:Chromatography, Liquid; D004987:Ethers / Q000737:chemistry / Q000378:metabolism*; D017353:Gene Deletion; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D048630:Polyketide Synthases / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D013141:Spiro Compounds / Q000737:chemistry / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics; D013869:Thiolester Hydrolases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004987:Ethers; D011994:Recombinant Proteins; D013141:Spiro Compounds; C452419:nanchangmycin; D048630:Polyketide Synthases; D013869:Thiolester Hydrolases