title: Δ(11,12) double bond formation in tirandamycin biosynthesis is atypically catalyzed by TrdE, a glycoside hydrolase family enzyme.
abstract: The tirandamycins (TAMs) are a small group of Streptomyces-derived natural products that target bacterial RNA polymerase. Within the TAM biosynthetic cluster, trdE encodes a glycoside hydrolase whose role in TAM biosynthesis has been undefined until now. We report that in vivo trdE inactivation leads to accumulation of pre-tirandamycin, the earliest intermediate released from its mixed polyketide/nonribosomal peptide biosynthetic assembly line. In vitro and site-directed mutagenesis studies showed that TrdE, a putative glycoside hydrolase, catalyzes in a highly atypical fashion the installation of the Δ(11,12) double bond during TAM biosynthesis.
authors.affiliation: CAS Key Laboratory of Marine Bio-resources Sustainable Utilization, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
authors.forename: Xuhua
authors.initials: X
authors.lastname: Mo
authors.forename: Junying
authors.initials: J
authors.lastname: Ma
authors.forename: Hongbo
authors.initials: H
authors.lastname: Huang
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Song
authors.forename: Si
authors.initials: S
authors.lastname: Zhang
authors.forename: Changsheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ju
mesh_terms: D000617:Aminoglycosides / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D002621:Chemistry / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006026:Glycoside Hydrolases / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000737:chemistry; D013302:Streptomyces / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors
chemical_list: D000617:Aminoglycosides; D001426:Bacterial Proteins; D010455:Peptides; C003608:tirandamycin A; D006026:Glycoside Hydrolases