Fluostatins M–Q Featuring a 6-5-6-6 Ring Skeleton and High Oxidized A-Rings from Marine Streptomyces sp. PKU-MA00045
Aromatic polyketides from marine actinomycetes have received increasing attention due to their unusual structures and potent bioactivities. Compared to their terrestrial counterparts, marine aromatic polyketides have been less discovered and their structural and biological diversities are far from b...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-03-01
|
| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1660-3397/16/3/87 |
| _version_ | 1818034821373362176 |
|---|---|
| author | Jing Jin Xiaoyan Yang Tan Liu Hua Xiao Guiyang Wang Mengjie Zhou Fawang Liu Yingtao Zhang Dong Liu Minghua Chen Wei Cheng Donghui Yang Ming Ma |
| author_facet | Jing Jin Xiaoyan Yang Tan Liu Hua Xiao Guiyang Wang Mengjie Zhou Fawang Liu Yingtao Zhang Dong Liu Minghua Chen Wei Cheng Donghui Yang Ming Ma |
| author_sort | Jing Jin |
| collection | DOAJ |
| description | Aromatic polyketides from marine actinomycetes have received increasing attention due to their unusual structures and potent bioactivities. Compared to their terrestrial counterparts, marine aromatic polyketides have been less discovered and their structural and biological diversities are far from being fully investigated. In this study, we employed a PCR-based genome mining method to discover aromatic polyketides in our marine bacteria collection. Five new atypical angucyclinones, fluostatins M–Q (1–5) featuring a unique 6-5-6-6 ring skeleton, were discovered from one “positive” Streptomyces sp. PKU-MA00045. The structures of fluostatins M–Q (1–5) were elucidated based on comprehensive spectroscopic analyses and the crystallographic structure of fluostatin P (4), which contains the most oxidized A-ring, was solved by X-ray diffraction analysis with Cu Kα radiation. Compared to the published 16 fluostatin analogues, fluostatins M–Q (1–5) contained a different methoxy group attached at C-7 and hydroxy group attached at C-4, enriching the structural diversity of aromatic polyketides from marine actinomycetes. Genome sequencing of Streptomyces sp. PKU-MA00045 revealed the biosynthetic gene cluster of fluostatins M–Q (1–5), which contained different genes and gene organizations compared to known fluostatin gene clusters, facilitating the investigation of the biosynthesis of the unique 6-5-6-6 ring skeleton in all fluostatins. |
| first_indexed | 2024-12-10T06:45:15Z |
| format | Article |
| id | doaj.art-6f860f2a8b424d06bdd74de7a0e67322 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-12-10T06:45:15Z |
| publishDate | 2018-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-6f860f2a8b424d06bdd74de7a0e673222022-12-22T01:58:41ZengMDPI AGMarine Drugs1660-33972018-03-011638710.3390/md16030087md16030087Fluostatins M–Q Featuring a 6-5-6-6 Ring Skeleton and High Oxidized A-Rings from Marine Streptomyces sp. PKU-MA00045Jing Jin0Xiaoyan Yang1Tan Liu2Hua Xiao3Guiyang Wang4Mengjie Zhou5Fawang Liu6Yingtao Zhang7Dong Liu8Minghua Chen9Wei Cheng10Donghui Yang11Ming Ma12State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Tiantanxili, Beijing 100050, ChinaState Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaAromatic polyketides from marine actinomycetes have received increasing attention due to their unusual structures and potent bioactivities. Compared to their terrestrial counterparts, marine aromatic polyketides have been less discovered and their structural and biological diversities are far from being fully investigated. In this study, we employed a PCR-based genome mining method to discover aromatic polyketides in our marine bacteria collection. Five new atypical angucyclinones, fluostatins M–Q (1–5) featuring a unique 6-5-6-6 ring skeleton, were discovered from one “positive” Streptomyces sp. PKU-MA00045. The structures of fluostatins M–Q (1–5) were elucidated based on comprehensive spectroscopic analyses and the crystallographic structure of fluostatin P (4), which contains the most oxidized A-ring, was solved by X-ray diffraction analysis with Cu Kα radiation. Compared to the published 16 fluostatin analogues, fluostatins M–Q (1–5) contained a different methoxy group attached at C-7 and hydroxy group attached at C-4, enriching the structural diversity of aromatic polyketides from marine actinomycetes. Genome sequencing of Streptomyces sp. PKU-MA00045 revealed the biosynthetic gene cluster of fluostatins M–Q (1–5), which contained different genes and gene organizations compared to known fluostatin gene clusters, facilitating the investigation of the biosynthesis of the unique 6-5-6-6 ring skeleton in all fluostatins.http://www.mdpi.com/1660-3397/16/3/87aromatic polyketidesfluostatinsgene clustergenome miningmarine actinomycetes |
| spellingShingle | Jing Jin Xiaoyan Yang Tan Liu Hua Xiao Guiyang Wang Mengjie Zhou Fawang Liu Yingtao Zhang Dong Liu Minghua Chen Wei Cheng Donghui Yang Ming Ma Fluostatins M–Q Featuring a 6-5-6-6 Ring Skeleton and High Oxidized A-Rings from Marine Streptomyces sp. PKU-MA00045 Marine Drugs aromatic polyketides fluostatins gene cluster genome mining marine actinomycetes |
| title | Fluostatins M–Q Featuring a 6-5-6-6 Ring Skeleton and High Oxidized A-Rings from Marine Streptomyces sp. PKU-MA00045 |
| title_full | Fluostatins M–Q Featuring a 6-5-6-6 Ring Skeleton and High Oxidized A-Rings from Marine Streptomyces sp. PKU-MA00045 |
| title_fullStr | Fluostatins M–Q Featuring a 6-5-6-6 Ring Skeleton and High Oxidized A-Rings from Marine Streptomyces sp. PKU-MA00045 |
| title_full_unstemmed | Fluostatins M–Q Featuring a 6-5-6-6 Ring Skeleton and High Oxidized A-Rings from Marine Streptomyces sp. PKU-MA00045 |
| title_short | Fluostatins M–Q Featuring a 6-5-6-6 Ring Skeleton and High Oxidized A-Rings from Marine Streptomyces sp. PKU-MA00045 |
| title_sort | fluostatins m q featuring a 6 5 6 6 ring skeleton and high oxidized a rings from marine streptomyces sp pku ma00045 |
| topic | aromatic polyketides fluostatins gene cluster genome mining marine actinomycetes |
| url | http://www.mdpi.com/1660-3397/16/3/87 |
| work_keys_str_mv | AT jingjin fluostatinsmqfeaturinga6566ringskeletonandhighoxidizedaringsfrommarinestreptomycessppkuma00045 AT xiaoyanyang fluostatinsmqfeaturinga6566ringskeletonandhighoxidizedaringsfrommarinestreptomycessppkuma00045 AT tanliu fluostatinsmqfeaturinga6566ringskeletonandhighoxidizedaringsfrommarinestreptomycessppkuma00045 AT huaxiao fluostatinsmqfeaturinga6566ringskeletonandhighoxidizedaringsfrommarinestreptomycessppkuma00045 AT guiyangwang fluostatinsmqfeaturinga6566ringskeletonandhighoxidizedaringsfrommarinestreptomycessppkuma00045 AT mengjiezhou fluostatinsmqfeaturinga6566ringskeletonandhighoxidizedaringsfrommarinestreptomycessppkuma00045 AT fawangliu fluostatinsmqfeaturinga6566ringskeletonandhighoxidizedaringsfrommarinestreptomycessppkuma00045 AT yingtaozhang fluostatinsmqfeaturinga6566ringskeletonandhighoxidizedaringsfrommarinestreptomycessppkuma00045 AT dongliu fluostatinsmqfeaturinga6566ringskeletonandhighoxidizedaringsfrommarinestreptomycessppkuma00045 AT minghuachen fluostatinsmqfeaturinga6566ringskeletonandhighoxidizedaringsfrommarinestreptomycessppkuma00045 AT weicheng fluostatinsmqfeaturinga6566ringskeletonandhighoxidizedaringsfrommarinestreptomycessppkuma00045 AT donghuiyang fluostatinsmqfeaturinga6566ringskeletonandhighoxidizedaringsfrommarinestreptomycessppkuma00045 AT mingma fluostatinsmqfeaturinga6566ringskeletonandhighoxidizedaringsfrommarinestreptomycessppkuma00045 |