Anaerobic Hydroxyproline Degradation Involving C-N Cleavage by a Glycyl Radical Enzyme

Yongxu Duan, Yifeng Wei, Meining Xing, Jiayi Liu, Li Jiang, Qiang Lu, Xumei Liu, Yanhong Liu, Ee Lui Ang, Rong Zhen Liao, Zhiguang Yuchi, Huimin Zhao, Yan Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Hydroxyprolines are highly abundant in nature as they are components of many structural proteins and osmolytes. Anaerobic degradation of trans-4-hydroxy-l-proline (t4L-HP) was previously found to involve the glycyl radical enzyme (GRE) t4L-HP dehydratase (HypD). Here, we report a pathway for anaerobic hydroxyproline degradation that involves a new GRE, trans-4-hydroxy-d-proline (t4D-HP) C-N-lyase (HplG). In this pathway, cis-4-hydroxy-l-proline (c4L-HP) is first isomerized to t4D-HP, followed by radical-mediated ring opening by HplG to give 2-amino-4-ketopentanoate (AKP), the first example of a ring opening reaction catalyzed by a GRE 1,2-eliminase. Subsequent cleavage by AKP thiolase (OrtAB) yields acetyl-CoA and d-alanine. We report a crystal structure of HplG in complex with t4D-HP at a resolution of 2.7 Å, providing insights into its catalytic mechanism. Different from HypD commonly identified in proline-reducing Clostridia, HplG is present in other types of fermenting bacteria, including propionate-producing bacteria, underscoring the diversity of enzymatic radical chemistry in the anaerobic microbiome.

Original languageEnglish (US)
Pages (from-to)9715-9722
Number of pages8
JournalJournal of the American Chemical Society
Volume144
Issue number22
DOIs
StatePublished - Jun 8 2022

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry

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