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Isocyanides as a Chemical Tool for Identifying [Fe]-Hydrogenase-Dependent Methanogenesis.

Created on 14 Sep 2026

Authors

Shunsuke Nomura, Seigo Shima

Published in

Chembiochem : a European journal of chemical biology. Volume 27. Issue 17. Pages e70535. Sep 14, 2026.

Abstract

In the hydrogenotrophic methanogens cultivated under nickel-sufficient standard medium (~5 µM Ni2+), two cytosolic [NiFe]-hydrogenases, F420-reducing hydrogenase (Frh) and heterodisulfide reductase (Hdr)-associating hydrogenase (Mvh), mainly provide electrons to the methanogenic pathway. In Methanothermobacter marburgensis under strictly nickel-limited conditions (< 50 nM Ni2+), which are encountered in certain natural environments, Frh and Mvh are strongly downregulated. Under these conditions, a coupled reaction with [Fe]-hydrogenase (Hmd) and F420-dependent methylene-tetrahydromethanopterin dehydrogenase (Mtd) substitutes for the function of Frh, where F420-dependent electron-donating protein (Elp) complexes with Hdr and donates electrons from the reduced form of F420 to Hdr. Thus, Hmd mainly provides electrons to methanogenesis in nickel-limited environments. In this study, to evaluate the potential of isocyanides as an Hmd-specific chemical tool to probe this pathway, we determined their inhibitory effects on the H2-dependent F420-reducing activity in the cell extract and on the in vitro methanogenesis reaction in a cell extract and in a cell suspension. Isocyanides specifically inhibited the activities of the samples from nickel-limited cells. The inhibitory effect on the cell suspension was strengthened by the use of a hydrophobic isocyanide. These results demonstrate their potential as a chemical tool for identifying in situ Hmd-dependent methanogenesis activity in natural environmental samples.

PMID:
42733968
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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