Characterization and heterologous expression of the neoabyssomicin/abyssomicin biosynthetic gene cluster from Streptomyces koyangensis SCSIO 5802
文献类型：期刊论文
| 作者 | Tu, JJ; Li, ST; Chen, J; Song, YX; Fu, SB; Ju, JH; Li, QL; liql@scsio.ac.cn |
| 刊名 | MICROBIAL CELL FACTORIES
 |
| 出版日期 | 2018 |
| 卷号 | 17页码:-28 |
| 英文摘要 | Background: The deep-sea-derived microbe Streptomyces koyangensis SCSIO 5802 produces neoabyssomicins A-B (1-2) and abyssomicins 2 (3) and 4 (4). Neoabyssomicin A (1) augments human immunodeficiency virus-1 (HIV-1) replication whereas abyssomicin 2 (3) selectively reactivates latent HIV and is also active against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus (MRSA). Structurally, neoabyssomicins A-B constitute a new subtype within the abyssomicin family and feature unique structural traits characteristic of extremely interesting biosynthetic transformations. Results: In this work, the biosynthetic gene cluster (BGC) for the neoabyssomicins and abyssomicins, composed of 28 opening reading frames, was identified in S. koyangensis SCSIO 5802, and its role in neoabyssomicin/abyssomicin biosynthesis was confirmed via gene inactivation and heterologous expression experiments. Bioinformatics and genomics analyses enabled us to propose a biosynthetic pathway for neoabyssomicin/abyssomicin biosynthesis. Similarly, a protective export system by which both types of compounds are secreted from the S. koyangensis producer was identified, as was a four-component ABC transporter-based import system central to neoabyssomicin/ abyssomicin biosynthesis. Furthermore, two regulatory genes, abmI and abmH, were unambiguously shown to be positive regulators of neoabyssomicin/abyssomicin biosynthesis. Consistent with their roles as positive regulatory genes, the overexpression of abmI and abmH (independent of each other) was shown to improve neoabyssomicin/ abyssomicin titers. Conclusions: These studies provide new insight into the biosynthesis of the abyssomicin class of natural products, and highlight important exploitable features of its BGC for future efforts. Elucidation of the neoabyssomicin/abyssomicin BGC now enables combinatorial biosynthetic initiatives aimed at improving both the titers and pharmaceutical properties of these important natural products-based drug leads. |
| 学科主题 | Biotechnology & Applied Microbiology |
| WOS关键词 | Abyssomicin ; Tetronate ; Biosynthesis ; Transporter ; Pathway-specific regulator |
| 资助项目 | LMB |
| 源URL | [http://ir.scsio.ac.cn/handle/344004/16999]  |
| 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 |
| 通讯作者 | liql@scsio.ac.cn |
| 推荐引用方式 GB/T 7714 | Tu, JJ,Li, ST,Chen, J,et al. Characterization and heterologous expression of the neoabyssomicin/abyssomicin biosynthetic gene cluster from Streptomyces koyangensis SCSIO 5802[J]. MICROBIAL CELL FACTORIES,2018,17:-28. |
| APA | Tu, JJ.,Li, ST.,Chen, J.,Song, YX.,Fu, SB.,...&liql@scsio.ac.cn.(2018).Characterization and heterologous expression of the neoabyssomicin/abyssomicin biosynthetic gene cluster from Streptomyces koyangensis SCSIO 5802.MICROBIAL CELL FACTORIES,17,-28. |
| MLA | Tu, JJ,et al."Characterization and heterologous expression of the neoabyssomicin/abyssomicin biosynthetic gene cluster from Streptomyces koyangensis SCSIO 5802".MICROBIAL CELL FACTORIES 17(2018):-28. |
入库方式： OAI收割
来源：南海海洋研究所
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