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Characterization and heterologous expression of the neoabyssomicin/abyssomicin biosynthetic gene cluster from Streptomyces koyangensis SCSIO 5802
Tu, JJ; Li, ST; Chen, J; Song, YX; Fu, SB; Ju, JH; Li, QL; liql@scsio.ac.cn
2018
Source PublicationMICROBIAL CELL FACTORIES
Volume17Pages:-28
AbstractBackground: 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.
Department[Tu, Jiajia; Li, Siting; Chen, Jiang; Song, Yongxiang; Ju, Jianhua; Li, Qinglian] Chinese Acad Sci, CAS Key Lab Trop Marine Bioresources & Ecol, Guangdong Key Lab Marine Mat Med, RNAM Ctr Marine Microbiol,South China Sea Inst Oc, 164 West Xingang Rd, Guangzhou 510301, Guangdong, Peoples R China; [Tu, Jiajia; Fu, Shaobin] Zunyi Med Univ, Sch Pharm, 201 Dalian Rd, Zunyi 563000, Peoples R China; [Li, Siting] Shenzhen Univ, Coll Bio & Marine Sci, 3688 Nanhai Ave, Shenzhen 518060, Peoples R China; [Chen, Jiang; Ju, Jianhua] Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 110039, Peoples R China
Subject AreaBiotechnology & Applied Microbiology
WOS KeywordAbyssomicin ; Tetronate ; Biosynthesis ; Transporter ; Pathway-specific regulator
Funding ProjectLMB
Document Type期刊论文
Identifierhttp://ir.scsio.ac.cn/handle/344004/16999
Collection中科院海洋生物资源可持续利用重点实验室
Corresponding Authorliql@scsio.ac.cn
Recommended Citation
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.
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