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Genome Sequencing of Streptomyces olivaceus SCSIO T05 and Activated Production of Lobophorin CR4 via Metabolic Engineering and Genome Mining

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CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China
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College of Oceanology, University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China
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Author to whom correspondence should be addressed.
Mar. Drugs 2019, 17(10), 593; https://doi.org/10.3390/md17100593
Received: 18 September 2019 / Revised: 12 October 2019 / Accepted: 16 October 2019 / Published: 20 October 2019
(This article belongs to the Special Issue Bioactive Marine Heterocyclic Compounds)
Marine-sourced actinomycete genus Streptomyces continues to be an important source of new natural products. Here we report the complete genome sequence of deep-sea-derived Streptomyces olivaceus SCSIO T05, harboring 37 putative biosynthetic gene clusters (BGCs). A cryptic BGC for type I polyketides was activated by metabolic engineering methods, enabling the discovery of a known compound, lobophorin CR4 (1). Genome mining yielded a putative lobophorin BGC (lbp) that missed the functional FAD-dependent oxidoreductase to generate the d-kijanose, leading to the production of lobophorin CR4 without the attachment of d-kijanose to C17-OH. Using the gene-disruption method, we confirmed that the lbp BGC accounts for lobophorin biosynthesis. We conclude that metabolic engineering and genome mining provide an effective approach to activate cryptic BGCs. View Full-Text
Keywords: genome sequencing; gene disruption; lobophorin; metabolic engineering; genome mining genome sequencing; gene disruption; lobophorin; metabolic engineering; genome mining
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MDPI and ACS Style

Zhang, C.; Ding, W.; Qin, X.; Ju, J. Genome Sequencing of Streptomyces olivaceus SCSIO T05 and Activated Production of Lobophorin CR4 via Metabolic Engineering and Genome Mining. Mar. Drugs 2019, 17, 593.

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