The biosynthesis of methanobactin

Grace E. Kenney, Laura M.K. Dassama, Maria Eirini Pandelia, Anthony S. Gizzi, Ryan J. Martinie, Peng Gao, Caroline J. DeHart, Luis F. Schachner, Owen S. Skinner, Soo Y. Ro, Xiao Zhu, Monica Sadek, Paul M. Thomas, Steven C. Almo, J. Martin Bollinger, Carsten Krebs, Neil L. Kelleher, Amy C. Rosenzweig

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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 languageEnglish (US)
Pages (from-to)1411-1416
Number of pages6
JournalScience
Volume359
Issue number6382
DOIs
StatePublished - Mar 23 2018

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    Kenney, G. E., Dassama, L. M. K., Pandelia, M. E., Gizzi, A. S., Martinie, R. J., Gao, P., DeHart, C. J., Schachner, L. F., Skinner, O. S., Ro, S. Y., Zhu, X., Sadek, M., Thomas, P. M., Almo, S. C., Bollinger, J. M., Krebs, C., Kelleher, N. L., & Rosenzweig, A. C. (2018). The biosynthesis of methanobactin. Science, 359(6382), 1411-1416. https://doi.org/10.1126/science.aap9437