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Peer-reviewed veterinary case report

Targeted Inactivation of an <i>α/β</i> Hydrolase Gene Enables Discovery of Heterodimeric Nenestatins.

Year:
2026
Authors:
Wei W et al.
Affiliation:
South China Sea Institute of Oceanology · China

Abstract

Nenestatins (NENs) belong to benzo[<i>b</i>]fluorene-containing atypical angucyclines, a structurally diverse class of microbial natural products. Bioinformatic analysis of the NEN biosynthetic gene cluster (<i>nes</i> BGC) from the deep-sea sediment-derived <i>Micromonospora echinospora</i> SCSIO 04089 implicated Nes5 as an <i>α/β</i> hydrolase. The targeted inactivation of the <i>nes5</i> gene led to the accumulation of five new analogs, NENs E-I (<b>1</b>-<b>5</b>), together with the known monomer homo-dehydrorabelomycin E (<b>6</b>). Their structures were elucidated by comprehensive spectroscopic analysis and electronic circular dichroism calculations. Notably, both NEN A and NEN B were absent in the Δ<i>nes5</i> mutant, indicating that Nes5 is essential for their biosynthesis; however, the exact function of Nes5 requires further exploration.

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Original publication: https://europepmc.org/article/MED/41892962