Abstract
Metal homeostasis poses a major challenge to microbes, which must acquire scarce elements for core metabolic processes. Methanobactin, an extensively modified copper-chelating peptide, was one of the earliest natural products shown to enable microbial acquisition of a metal other than iron. We describe the core biosynthetic machinery responsible for the characteristic posttranslational modifications that grant methanobactin its specificity and affinity for copper. A heterodimer comprising MbnB, a DUF692 family iron enzyme, and MbnC, a protein from a previously unknown family, performs a dioxygen-dependent four-electron oxidation of the precursor peptide (MbnA) to install an oxazolone and an adjacent thioamide, the characteristic methanobactin bidentate copper ligands. MbnB and MbnC homologs are encoded together and separately in many bacterial genomes, suggesting functions beyond their roles in methanobactin biosynthesis.
Original language | English (US) |
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Pages (from-to) | 1411-1416 |
Number of pages | 6 |
Journal | Science |
Volume | 359 |
Issue number | 6382 |
DOIs | |
State | Published - Mar 23 2018 |
Funding
Supported by NIH grants GM118035 (A.C.R.), R01AT009143 (N.L.K.), U54-GM094662, U54 GM093342, P01 GM118303 (S.C.A.), R00GM111978 (M.-E.P.), and F32GM110934 (L.M.K.D.), as well as NSF grants MCB0842366 (A.C.R.) and MCB1330784 (J.M.B. and C.K.) and the Price Foundation (S.C.A.). G.E.K. was supported by American Heart Association grant 14PRE20460104. L.M.K.D. was additionally funded by a Postdoctoral Enrichment Program grant from the Burroughs Wellcome Fund. L.F.S. was supported by NIH grant T32GM105538 and a Howard Hughes Medical Institute Gilliam Fellowship. O.S.S. was supported by NSF GRFP grant 2014171659 and R.J.M. under NSF grant DGE1255832. At Northwestern University, the Quantitative Bio-element Imaging Center is supported by NASA Ames Research Center grant NNA06CB93G, the Proteomics Center for Excellence is supported by National Resource for Translational and Developmental Proteomics under NIH grant P41 GM108569 and National Cancer Institute (NCI) grant CCSG P30 CA060553, the Integrated Supported by NIH grants GM118035 (A.C.R.), R01AT009143 (N.L.K.), U54-GM094662, U54 GM093342, P01 GM118303 (S.C.A.), R00GM111978 (M.-E.P.), and F32GM110934 (L.M.K.D.), as well as NSF grants MCB0842366 (A.C.R.) and MCB1330784 (J.M.B. and C.K.) and the Price Foundation (S.C.A.). G.E.K. was supported by American Heart Association grant 14PRE20460104. L.M.K.D. was additionally funded by a Postdoctoral Enrichment Program grant from the Burroughs Wellcome Fund. L.F.S. was supported by NIH grant T32GM105538 and a Howard Hughes Medical Institute Gilliam Fellowship. O.S.S. was supported by NSF GRFP grant 2014171659 and R.J.M. under NSF grant DGE1255832. At Northwestern University, the Quantitative Bio-element Imaging Center is supported by NASA Ames Research Center grant NNA06CB93G, the Proteomics Center for Excellence is supported by National Resource for Translational and Developmental Proteomics under NIH grant P41 GM108569 and National Cancer Institute (NCI) grant CCSG P30 CA060553, the Integrated Molecular Structure Education and Research Center is supported by Northwestern University and the State of Illinois, the International Institute for Nanotechnology, and the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF grant NNCI-1542205), and the Keck Biophysics Facility is supported in part by NCI Cancer Center Support Grant CA060553. Some work was performed at the Albert Einstein Anaerobic Structural and Functional Genomics Resource. All authors declare no conflicts of interest. All data are presented in the supplementary materials. Molecular Structure Education and Research Center is supported by Northwestern University and the State of Illinois, the International Institute for Nanotechnology, and the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF grant NNCI-1542205), and the Keck Biophysics Facility is supported in part by NCI Cancer Center Support Grant CA060553. Some work was performed at the Albert Einstein Anaerobic Structural and Functional Genomics Resource. All authors declare no conflicts of interest. All data are presented in the supplementary materials.
ASJC Scopus subject areas
- General