利用靶向II型聚酮合酶的PCR技术从海洋放线菌中发现angucyclinone聚酮类天然产物

doi:10.5246/jcps.2017.03.017

中国药学(英文版) ›› 2017, Vol. 26 ›› Issue (3): 173-179.DOI: 10.5246/jcps.2017.03.017

利用靶向II型聚酮合酶的PCR技术从海洋放线菌中发现angucyclinone聚酮类天然产物

杨小燕, 金晶, 周梦洁, 许青霞, 刘发旺, 张英涛, 马明^*, 杨东辉^*

北京大学医学部药学院天然药物及仿生药物国家重点实验室, 北京 100191

收稿日期:2016-11-28 修回日期:2016-12-26 出版日期:2017-03-30 发布日期:2017-01-13
通讯作者: Tel.: +86-010-82801559, E-mail: mma@bjmu.edu.cn, ydhui@bjmu.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 81573326).

Discovery of angucyclinone polyketides from marine actinomycetes with a genomic DNA-based PCR assay targeting type II polyketide synthase

Xiaoyan Yang, Jing Jin, Mengjie Zhou, Qingxia Xu, Fawang Liu, Yingtao Zhang, Ming Ma^*, Donghui Yang^*

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2016-11-28 Revised:2016-12-26 Online:2017-03-30 Published:2017-01-13
Contact: Tel.: +86-010-82801559, E-mail: mma@bjmu.edu.cn, ydhui@bjmu.edu.cn
Supported by:
National Natural Science Foundation of China (Grant No. 81573326).

摘要/Abstract

摘要：

Angucyclinones是一类主要由陆地放线菌产生的芳香聚酮类化合物, 其生物合成主要是由II型聚酮合酶(PKS)催化完成。为了在海洋放线菌中探索此类芳香聚酮类化合物, 我们以167株海洋放线菌基因组DNA为模板, 对含有II型聚酮合酶的菌株进行了PCR筛选, 通过对PCR产物测序验证, 确定了12株阳性菌株。通过大规模发酵培养和色谱分离、波谱鉴定, 从阳性菌株Streptomyces sp. PKU-MA00218中发现了四个angucyclinone芳香聚酮类化合物, 6-deoxy-8-O-methylrabelomycin (1), 8-O-methylrabelomycin (2), 8-O-methyltetrangulol (3), 和angucyclinone C 的C环裂解产物 (4)。化合物4为首次从海洋放线菌中分离得到。Angucyclinone芳香聚酮1–4的发现展示了基于生物合成的基因组挖掘技术在天然产物探索发现中的重要作用。

关键词: Angucyclinone, 芳香聚酮, 基因组挖掘, 海洋放线菌, II型聚酮合酶

Abstract:

Angucyclinones are aromatic polyketides produced by type II polyketide synthases (PKS) and are mainly found in terrestrial actinomycetes. To discover more angucyclinones from marine actinomycetes, a genomic DNA-based PCR assay targeting type II polyketide synthases was performed. Among the 167 marine actinomycetes strains screened, twelve strains were identified as the “positive” strains possessing type II PKS-encoding genes based on the sequencing of PCR products. One of the 12 “positive” strains, Streptomyces sp. PKU-MA00218 was selected for the large-scale fermentation based on the HPLC and TLC analysis. Four angucyclinones, 6-deoxy-8-O-methylrabelomycin (1), 8-O-methylrabelomycin (2), 8-O-methyltetrangulol (3), C-ring cleavage product of angucyclinone C (4), were isolated and their structures were elucidated based on spectroscopic analyses. The isolation of angucyclinones 1–4 highlights the power of genome mining technologies based on biosynthetic knowledge in natural products discovery.

Key words: Angucyclinone, Aromatic polyketides, Genome mining, Marine actinomycetes, Type II polyketide synthases

中图分类号:

R931.77

Supporting:

杨小燕, 金晶, 周梦洁, 许青霞, 刘发旺, 张英涛, 马明, 杨东辉. 利用靶向II型聚酮合酶的PCR技术从海洋放线菌中发现angucyclinone聚酮类天然产物[J]. 中国药学(英文版), 2017, 26(3): 173-179.

Xiaoyan Yang, Jing Jin, Mengjie Zhou, Qingxia Xu, Fawang Liu, Yingtao Zhang, Ming Ma, Donghui Yang. Discovery of angucyclinone polyketides from marine actinomycetes with a genomic DNA-based PCR assay targeting type II polyketide synthase[J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(3): 173-179.

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利用靶向II型聚酮合酶的PCR技术从海洋放线菌中发现angucyclinone聚酮类天然产物

Discovery of angucyclinone polyketides from marine actinomycetes with a genomic DNA-based PCR assay targeting type II polyketide synthase

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