title: A Single Gene Cluster for Chalcomycins and Aldgamycins: Genetic Basis for Bifurcation of Their Biosynthesis.
abstract: Aldgamycins are 16-membered macrolide antibiotics with a rare branched-chain sugar d-aldgarose or decarboxylated d-aldgarose at C-5. In our efforts to clone the gene cluster for aldgamycins from a marine-derived Streptomyces sp. HK-2006-1 capable of producing both aldgamycins and chalcomycins, we found that both are biosynthesized from a single gene cluster. Whole-genome sequencing combined with gene disruption established the entire gene cluster of aldgamycins: nine new genes are incorporated with the previously identified chalcomycin gene cluster. Functional analysis of these genes revealed that almDI/almDII, (encoding α/β subunits of pyruvate dehydrogenase) triggers the biosynthesis of aldgamycins, whereas almCI (encoding an oxidoreductase) initiates chalcomycins biosynthesis. This is the first report that aldgamycins and chalcomycins are derived from a single gene cluster and of the genetic basis for bifurcation in their biosynthesis.
authors.affiliation: College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Tang
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, No. 601 Huangpu Avenue, Guangzhou, 510632, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Dai
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, No. 601 Huangpu Avenue, Guangzhou, 510632, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Gao
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, No. 601 Huangpu Avenue, Guangzhou, 510632, China.
authors.forename: Chuan-Xi
authors.initials: CX
authors.lastname: Wang
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, No. 601 Huangpu Avenue, Guangzhou, 510632, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Chen
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, No. 185 Donghu Road, Wuhan, 430071, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Hong
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, No. 601 Huangpu Avenue, Guangzhou, 510632, China. thudan@jnu.edu.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.affiliation: College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang, 110016, China. tyaoxs@jnu.edu.cn.|Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, No. 601 Huangpu Avenue, Guangzhou, 510632, China. tyaoxs@jnu.edu.cn.
authors.forename: Xin-Sheng
authors.initials: XS
authors.lastname: Yao
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D003837:Deoxy Sugars / Q000096:biosynthesis; D005798:Genes, Bacterial; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism*; D005810:Multigene Family / Q000235:genetics*; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000235:genetics; D013302:Streptomyces / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D003837:Deoxy Sugars; D018942:Macrolides; D030481:Pyruvate Dehydrogenase (Lipoamide)
keywords: aldgamycins; aldgarose; antibiotics; biosynthesis; chalcose