title: Identification and characterization of xiamycin A and oxiamycin gene cluster reveals an oxidative cyclization strategy tailoring indolosesquiterpene biosynthesis.
abstract: Xiamycin A (XMA) and oxiamycin (OXM) are bacterial indolosesquiterpenes featuring rare pentacyclic ring systems and are isolated from a marine-derived  Streptomyces  sp. SCSIO 02999. The putative biosynthetic gene cluster for XMA/OXM was identified by a partial genome sequencing approach. Eighteen genes were proposed to be involved in XMA/OXM biosynthesis, including five genes for terpene synthesis via a non-mevalonate pathway, eight genes encoding oxidoreductases, and five genes for regulation and resistance. Targeted disruptions of 13 genes within the xia gene cluster were carried out to probe their encoded functions in XMA/OXM biosynthesis. The disruption of xiaK, encoding an aromatic ring hydroxylase, led to a mutant producing indosespene and a minor amount of XMA. Feeding of indosespene to XMA/OXM nonproducing mutants revealed indosespene as a common precursor for XMA/OXM biosynthesis. Most notably, the flavin dependent oxygenase XiaI was biochemically characterized in vitro to convert indosespene to XMA, revealing an unusual oxidative cyclization strategy tailoring indolosesquiterpene 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: Huixian
authors.initials: H
authors.lastname: Li
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Zhang
authors.forename: Sumei
authors.initials: S
authors.lastname: Li
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Guangtao
authors.initials: G
authors.lastname: Zhang
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.forename: Xinpeng
authors.initials: X
authors.lastname: Tian
authors.forename: Si
authors.initials: S
authors.lastname: Zhang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ju
authors.forename: Changsheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D055162:Biocatalysis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003500:Cyclization; D015964:Gene Expression Regulation, Bacterial; D005810:Multigene Family; D009154:Mutation; D010084:Oxidation-Reduction; D012717:Sesquiterpenes / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D012717:Sesquiterpenes; C556785:xiamycin