RESEARCH ARTICLE Lipoate-binding proteins and specific lipoate-protein ligases in microbial sulfur oxidation reveal an atpyical role for an old cofactor Xinyun Cao1†‡, Tobias Koch2†, Lydia Steffens2, Julia Finkensieper2, Renate Zigann2, John E Cronan1,3, Christiane Dahl2* 1Department of Biochemistry, University of Illinois, Urbana, United States; 2Institut fu¨ r Mikrobiologie and Biotechnologie, Rheinische Friedrich-Wilhelms-Universita¨ t Bonn, Bonn, Germany; 3Department of Microbiology, University of Illinois, Urbana, United States Abstract Many Bacteria and Archaea employ the heterodisulfide reductase (Hdr)-like sulfur oxidation pathway. The relevant genes are inevitably associated with genes encoding lipoate- binding proteins (LbpA). Here, deletion of the gene identified LbpA as an essential component of the Hdr-like sulfur-oxidizing system in the Alphaproteobacterium Hyphomicrobium denitrificans. *For correspondence: Thus, a biological function was established for the universally conserved cofactor lipoate that is
[email protected] markedly different from its canonical roles in central metabolism. LbpAs likely function as sulfur- binding entities presenting substrate to different catalytic sites of the Hdr-like complex, similar to †These authors contributed the substrate-channeling function of lipoate in carbon-metabolizing multienzyme complexes, for equally to this work example pyruvate dehydrogenase. LbpAs serve a specific function in sulfur oxidation, cannot ‡ Present address: Department functionally replace the related GcvH protein in Bacillus subtilis and are not modified by the of Biochemistry, University of canonical E. coli and B. subtilis lipoyl attachment machineries. Instead, LplA-like lipoate-protein Wisconsin-Madison, Madison, ligases encoded in or in immediate vicinity of hdr-lpbA gene clusters act specifically on these United States proteins. Competing interests: The DOI: https://doi.org/10.7554/eLife.37439.001 authors declare that no competing interests exist.