Bacterial copper acquisition

Abstract

Methanotrophic bacteria use methane, a potent greenhouse gas, as their primary source of carbon and energy. The first step in methane metabolism is its oxidation to methanol. In mostly all methanotrophs, this chemically challenging reaction is catalyzed by particulate methane monooxygenase (pMMO), a copper‐dependent integral membrane enzyme. Many methanotrophs acquire copper for pMMO by secreting small ribosomally produced, post‐translationally modified natural products called methanobactins. Each species produces a methanobactin (Mbn) with a unique structure, and all Mbns characterized thus far bind copper with high affinity. The copper‐loaded form (CuMbn) is then re‐internalized into the cell via an active transport process. Genome mining has led to the identification of operons containing potential Mbn biosynthesis, transport, and regulatory genes. These operons are present in a range of non‐methanotrophic bacteria as well, suggesting a broader role for Mbn and Mbn‐like molecules in and perhaps beyond copper acquisition. The roles of specific gene products have been investigated by genetic, biophysical, and structural approaches. These data provide evidence for CuMbn‐protein interactions and begin to elucidate the molecular mechanisms of its recognition, transport, and biosynthesis.Support or Funding InformationThis work was supported by NIH grants GM118035 (A. C. R.) and F32GM110934 (L. M. K. D.), a Burroughs Wellcome Fund PDEP award (L. M. K. D.), and AHA grant 14PRE20460104 (G. E. K.).