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bioRxiv · 10.1101/2024.12.20.629799

Discovery and Biosynthesis of Nyuzenamides D and E by Genome Mining in Streptomyces hygroscopicus

Lum, K. Y.·Kumar, R.·Yang, Z.·Souza, L. D. O.·Jarmusch, S. A.·Moreira, J. M. A.·Morth, J. P.·Ding, L.
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Abstract

Nyuzenamides belong to the class of bioactive cinnamoyl moiety containing non-ribosomal peptides (NRPs). However, their biosynthetic gene cluster (BGC) remains unconfirmed. Genome-mining revealed a putative nyu BGC in Streptomyces hygroscopicus DSM 40578. Nyuzenamides D (1) and E (2) were subsequently isolated, and the structures were elucidated by detailed NMR spectroscopic and MS spectrometric data analyses. The absolute configuration of 1 was determined by a single-crystal X-ray diffraction study. Through retro-biosynthesis and CRISPR-genome editing, the non-ribosomal peptide synthetase biosynthetic gene cluster for nyuzenamides was confirmed. Our discovery enriches the diversity of cinnamoyl-containing nonribosomal peptides and validates the biosynthetic gene clusters for future genome-mining research.

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Lum, K. Y., Kumar, R., Yang, Z., Souza, L. D. O., Jarmusch, S. A., Moreira, J. M. A., Morth, J. P., Ding, L.. 2024-12-21. Discovery and Biosynthesis of Nyuzenamides D and E by Genome Mining in Streptomyces hygroscopicus. https://doi.org/10.1101/2024.12.20.629799

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