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

• Main Authors: Chunyan Zhang, Wenjuan Ding, Xiangjing Qin, Jianhua Ju
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: Marine Drugs
• Subjects: genome sequencing; gene disruption; lobophorin; metabolic engineering; genome mining
• Online Access: https://www.mdpi.com/1660-3397/17/10/593

Marine-sourced actinomycete genus <i>Streptomyces</i> continues to be an important source of new natural products. Here we report the complete genome sequence of deep-sea-derived <i>Streptomyces olivaceus</i> 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 (<b>1</b>). Genome mining yielded a putative lobophorin BGC (<i>lbp</i>) that missed the functional FAD-dependent oxidoreductase to generate the <span style="font-variant: small-caps;">d</span>-kijanose, leading to the production of lobophorin CR4 without the attachment of <span style="font-variant: small-caps;">d</span>-kijanose to C17-OH. Using the gene-disruption method, we confirmed that the <i>lbp</i> BGC accounts for lobophorin biosynthesis. We conclude that metabolic engineering and genome mining provide an effective approach to activate cryptic BGCs.