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DOI | 10.1038/s41467-018-06622-2 |
Biosynthesis of helvolic acid and identification of an unusual C-4-demethylation process distinct from sterol biosynthesis | |
Lv, Jian-Ming1; Hu, Dan1; Gao, Hao1; Kushiro, Tetsuo2; Awakawa, Takayoshi2; Chen, Guo-Dong1; Wang, Chuan-Xi1; Abe, Ikuro2; Yao, Xin-Sheng1 | |
2017-11-21 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | Peoples R China; Japan |
英文摘要 | Fusidane-type antibiotics represented by helvolic acid, fusidic acid and cephalosporin P1 are a class of bacteriostatic agents, which have drawn renewed attention because they have no cross-resistance to commonly used antibiotics. However, their biosynthesis is poorly understood. Here, we perform a stepwise introduction of the nine genes from the proposed gene cluster for helvolic acid into Aspergillus oryzae NSAR1, which enables us to isolate helvolic acid (-20 mg L-1) and its 21 derivatives. Anti-Staphylococcus aureus assay reveals that the antibacterial activity of three intermediates is even stronger than that of helvolic acid. Notably, we observe an unusual C-4 demethylation process mediated by a promiscuous short-chain dehydrogenase/reductase ( HelC) and a cytochrome P450 enzyme ( HelB1), which is distinct from the common sterol biosynthesis. These studies have set the stage for using biosynthetic approaches to expand chemical diversity of fusidane-type antibiotics. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000416039000012 |
WOS关键词 | FUSIDIC ACID ; SACCHAROMYCES-CEREVISIAE ; ASPERGILLUS-FUMIGATUS ; GENE ; OXIDOSQUALENE ; ANTIBIOTICS ; CYCLIZATION ; PATHWAYS ; SQUALENE ; ORYZAE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204027 |
专题 | 资源环境科学 |
作者单位 | 1.Jinan Univ, Guangdong Prov Key Lab Pharmacodynam Constituents, Coll Pharm, Inst Tradit Chinese Med & Nat Prod, Guangzhou 510632, Guangdong, Peoples R China; 2.Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan |
推荐引用方式 GB/T 7714 | Lv, Jian-Ming,Hu, Dan,Gao, Hao,et al. Biosynthesis of helvolic acid and identification of an unusual C-4-demethylation process distinct from sterol biosynthesis[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Lv, Jian-Ming.,Hu, Dan.,Gao, Hao.,Kushiro, Tetsuo.,Awakawa, Takayoshi.,...&Yao, Xin-Sheng.(2017).Biosynthesis of helvolic acid and identification of an unusual C-4-demethylation process distinct from sterol biosynthesis.NATURE COMMUNICATIONS,8. |
MLA | Lv, Jian-Ming,et al."Biosynthesis of helvolic acid and identification of an unusual C-4-demethylation process distinct from sterol biosynthesis".NATURE COMMUNICATIONS 8(2017). |
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