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Isolation and structure elucidation of lipopeptide antibiotic taromycin B from the activated taromycin biosynthetic gene cluster


In the ongoing effort to unlock the chemical potential of marine bacteria, genetic engineering of biosynthetic gene clusters (BGCs) is increasingly used to awake or improve expression of biosynthetic genes that may lead to discovery of novel bioactive natural products. Previously, we reported the successful capture, engineering and heterologous expression of an orphan BGC from the marine actinomycete Saccharomonospora sp. CNQ-490, which resulted in the isolation of the novel lipopeptide antibiotic taromycin A. Herein we report the isolation and structure elucidation of taromycin B, the second most abundant product of the taromycin biosynthetic series, and show that taromycins A and B exhibit complex chromatographic properties indicative of interconverting conformations. Taromycins A and B display potent activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium clinical isolates, suggestive that the taromycin molecular scaffold is a promising starting point for further derivatization to produce compounds with promising antibiotic characteristics.

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We are grateful to PR Jensen and W Fenical for providing Saccharomonospora sp. CNQ-490, M Bibb for S. coelicolor M1146, RD Kersten for assistance with MS analysis, BM Dungan for assistance with NMR, X Tang and PA Jordan for helpful discussions. This work was supported by grants from the National Institutes of Health (R01-GM085770 to BSM, U01-AI124316 to VN and Instrument Grant S10-OD010640).

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Correspondence to Bradley S Moore.

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Supplementary Information accompanies the paper on The Journal of Antibiotics website

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Reynolds, K., Luhavaya, H., Li, J. et al. Isolation and structure elucidation of lipopeptide antibiotic taromycin B from the activated taromycin biosynthetic gene cluster. J Antibiot 71, 333–338 (2018).

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