**Chunyan Zhang 1,2, Wenjuan Ding 1,2, Xiangjing Qin <sup>1</sup> and Jianhua Ju 1,2,\***


Received: 18 September 2019; Accepted: 16 October 2019; Published: 20 October 2019

**Abstract:** 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.

**Keywords:** genome sequencing; gene disruption; lobophorin; metabolic engineering; genome mining
