ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microbial Physiology and Metabolism
Hydrogen sulfide acts as a sulfur source for iron sulfur cluster biosynthesis in cysteine desulfurase-deficient E. coli under anaerobic conditions
Provisionally accepted
Heng Li
Jun Wang
Xiaorui Li
Guanya JiaHaisheng GanYanxiong WangZhiwei MaZhilong Zhu
Xiaoya Shang
Weining Niu*- School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The cysteine desulfurase (IscS) is a core component of the ISC iron-sulfur (Fe-S) cluster assembly system in E. coli. Deficiency of IscS leads to serious growth defects in E. coli, along with reduced activity of Fe-S cluster-dependent enzymes. We previously demonstrated that the growth defect of IscS-deficient E. coli (ΔiscS) is completely restored by H₂S exposure, but the underlying molecular mechanism was not fully understood. Here, based on proteomic analysis, we identified 19 up-regulated Fe-S proteins in the ΔiscS mutant upon H₂S exposure, 13 of which are involved with energy metabolism. Correspondingly, H₂S exposure also enhanced the activity of Fe-S enzymes in the mutant. Metabolomic analysis revealed a remarkable increase in the levels of the energy metabolites NAD⁺, succinate, and leucine. These results implied that H2S could restore cell proliferation and Fe-S cluster biosynthesis by compensating for the functional loss of IscS. We also constructed a series of mutants, each lacking a single component of the ISC assembly system. A key observation was that the ΔiscU mutant, deficient in the Fe-S cluster scaffold protein IscU, failed to have its growth defect rescued by H₂S exposure. These findings indicated that H2S promotes Fe-S cluster biosynthesis on IscU, ruling out direct assembly on apoproteins. Moreover, Na₂S supplementation during recombinant expression of aconitase B in the ΔiscS mutant significantly increased its Fe-S cluster abundance and enzymatic activity. We also demonstrated that, unlike the ΔiscS mutant, deletion of sufS, which encodes the cysteine desulfurase of the SUF Fe-S cluster biogenesis system, did not significantly impair bacterial growth, and the resulting mutant's proliferation was not affected by H₂S exposure. Our study elucidates the mechanism by which H₂S exposure rescues the proliferation impairment of the ΔiscS mutant. Specifically, we demonstrate that H₂S functions as a sulfur donor for Fe-S cluster assembly, thereby compensating for the biosynthetic deficit.
Keywords: Anaerobic conditions, cysteine desulfurase IscS, Escherichia coli, Hydrogen Sulfide, iron-sulfur cluster, scaffold protein IscU
Received: 03 Dec 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Li, Wang, Li, Jia, Gan, Wang, Ma, Zhu, Shang and Niu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Weining Niu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.