A Single Gene Cluster for Chalcomycins and Aldgamycins: Genetic Basis for Bifurcation of Their Biosynthesis |
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| Authors: | Xiao‐Long Tang Ping Dai Prof?Dr Hao Gao Dr Chuan‐Xi Wang Dr Guo‐Dong Chen Prof?Dr Kui Hong Dr Dan Hu Prof?Dr Xin‐Sheng Yao |
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| Affiliation: | 1. College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China;2. Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China;3. Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China |
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| 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. |
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| Keywords: | aldgamycins aldgarose antibiotics biosynthesis chalcose |
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