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.
Highlights
Produced natural products (NPs) are an important reservoir of therapeutic and agricultural agents [1]
In order to estimate the biosynthetic potential of S. olivaceus SCSIO T05, the complete genome was re-sequenced and acquired by the single-molecule real-time (SMRT) sequencing technology (PacBio)
A total of 67156 filtered reads with high-quality data of 432570025 bp were generated, and they were assembled into a linear contig by the hierarchical genome assembly process (HGAP) [20]
Summary
Produced natural products (NPs) are an important reservoir of therapeutic and agricultural agents [1]. The production of nocardamine [5] and atratumycin [6] in Streptomyces atratus SCSIO ZH16 was turned on via metabolic engineering These genome-based studies exemplify the benefits of genome mining and metabolic engineering used for activating cryptic BGCs and discovering new bioactive NPs. Lobophorins (Supporting Information (SI), Figure S1) belonging to a large class of spirotetronate antibiotics structurally feature a tetronate moiety spiro-linked with a cyclohexene ring, which is called pentacyclic aglycon or kijanolide [7,8,9,10,11,12,13,14,15,16,17]. CR4 (1); and (iii) identification of the lbp BGC housed in S. olivaceus SCSIO T05 by gene-disruption experiment and bioinformatics analysis
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