Activation and characterization of a cryptic gene cluster reveals a cyclization cascade for polycyclic tetramate macrolactams
文献类型：期刊论文
| 作者 | Saha, S; Zhang, WJ; Zhang, GT; Zhu, YG; Chen, YC; Liu, W; Yuan, CS; Zhang, QB; Zhang, HB; Zhang, LP |
| 刊名 | CHEMICAL SCIENCE
 |
| 出版日期 | 2017 |
| 卷号 | 8期号:2页码:1607-1612 |
| 通讯作者 | czhang2006@gmail.com |
| 中文摘要 | Polycyclic tetramate macrolactams (PTMs) are a growing class of natural products and are derived from a hybrid polyketide synthase (PKS)/non-ribosomal peptide synthetase (NRPS) pathway. PTM biosynthetic gene clusters are conserved and widely distributed in bacteria, however, most of them remain silent. Herein we report the activation of a PTM gene cluster in marine-derived Streptomyces pactum SCSIO 02999 by promoter engineering and heterologous expression, leading to the discovery of six new PTMs, pactamides A-F (11-16), with potent cytotoxic activity upon several human cancer cell lines. In vivo gene disruption experiments and in vitro biochemical assays reveal a reductive cyclization cascade for polycycle formation, with reactions sequentially generating the 5, 5/5 and 5/5/6 carbocyclic ring systems, catalysed by the phytoene dehydrogenase PtmB2, the oxidoreductase PtmB1, and the alcohol dehydrogenase PtmC, respectively. Furthermore, PtmC was demonstrated as a bifunctional cyclase for catalyzing the formation of the inner five-membered ring in ikarugamycin. This study suggests the possibility of finding more bioactive PTMs by genome mining and discloses a general mechanism for the formation of 5/5/6-type carbocyclic rings in PTMs. |
| 源URL | [http://ir.scsio.ac.cn/handle/344004/16219]  |
| 专题 | 南海海洋研究所_中科院海洋生物资源可持续利用重点实验室 |
| 推荐引用方式 GB/T 7714 | Saha, S,Zhang, WJ,Zhang, GT,et al. Activation and characterization of a cryptic gene cluster reveals a cyclization cascade for polycyclic tetramate macrolactams[J]. CHEMICAL SCIENCE,2017,8(2):1607-1612. |
| APA | Saha, S.,Zhang, WJ.,Zhang, GT.,Zhu, YG.,Chen, YC.,...&Zhang, CS.(2017).Activation and characterization of a cryptic gene cluster reveals a cyclization cascade for polycyclic tetramate macrolactams.CHEMICAL SCIENCE,8(2),1607-1612. |
| MLA | Saha, S,et al."Activation and characterization of a cryptic gene cluster reveals a cyclization cascade for polycyclic tetramate macrolactams".CHEMICAL SCIENCE 8.2(2017):1607-1612. |
入库方式： OAI收割
来源：南海海洋研究所
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