Repurposed HisC Aminotransferases Complete the Biosynthesis of Some Methanobactins

Yun Ji Park, Grace E. Kenney, Luis F. Schachner, Neil L. Kelleher, Amy C. Rosenzweig*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Methanobactins (Mbns) are ribosomally produced, post-translationally modified bacterial natural products with a high affinity for copper. MbnN, a pyridoxal 5′-phosphate-dependent aminotransferase, performs a transamination reaction that is the last step in the biosynthesis of Mbns produced by several Methylosinus species. Our bioinformatic analyses indicate that MbnNs likely derive from histidinol-phosphate aminotransferases (HisCs), which play a key role in histidine biosynthesis. A comparison of the HisC active site with the predicted MbnN structure suggests that MbnN's active site is altered to accommodate the larger and more hydrophobic substrates necessary for Mbn biosynthesis. Moreover, we have confirmed that MbnN is capable of catalyzing the final transamination step in Mbn biosynthesis in vitro and in vivo. We also demonstrate that without this final modification, Mbn exhibits significantly decreased stability under physiological conditions. An examination of other Mbns and Mbn operons suggests that N-terminal protection of this family of natural products is of critical importance and that several different means of N-terminal stabilization have evolved independently in Mbn subfamilies.

Original languageEnglish (US)
Pages (from-to)3515-3523
Number of pages9
JournalBiochemistry
Volume57
Issue number25
DOIs
StatePublished - Jun 26 2018

ASJC Scopus subject areas

  • Biochemistry

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