Characterization of a Dehydratase and Methyltransferase in the Biosynthesis of Ribosomally Synthesized and Post-translationally Modified Peptides in Lachnospiraceae

Liujie Huo, Xiling Zhao, Jeella Z. Acedo, Paola Estrada, Satish K. Nair, Wilfred A. van der Donk

Research output: Contribution to journalArticle

Abstract

As a result of the exponential increase in genomic data, discovery of novel ribosomally synthesized and post-translationally modified peptide natural products (RiPPs) has progressed rapidly in the past decade. The lanthipeptides are a major subset of RiPPs. Through genome mining we identified a novel lanthipeptide biosynthetic gene cluster (lah) from Lachnospiraceae bacterium C6A11, an anaerobic bacterium that is a member of the human microbiota and which is implicated in the development of host disease states such as type 2 diabetes and resistance to Clostridium difficile colonization. The lah cluster encodes at least seven putative precursor peptides and multiple post-translational modification (PTM) enzymes. Two unusual class II lanthipeptide synthetases LahM1/M2 and a substrate-tolerant S-adenosyl-l-methionine (SAM)-dependent methyltransferase LahSB are biochemically characterized in this study. We also present the crystal structure of LahSB in complex with product S-adenosylhomocysteine. This study sets the stage for further exploration of the final products of the lah pathway as well as their potential physiological functions in human/animal gut microbiota.

Original languageEnglish (US)
Pages (from-to)190-199
Number of pages10
JournalChemBioChem
Volume21
Issue number1-2
DOIs
StatePublished - Jan 15 2020

Fingerprint

Hydro-Lyases
Biosynthesis
Methyltransferases
Bacteria
Genes
S-Adenosylhomocysteine
Clostridium
Peptides
Anaerobic Bacteria
Clostridium difficile
Microbiota
Post Translational Protein Processing
Ligases
Multigene Family
Medical problems
Biological Products
Methionine
Type 2 Diabetes Mellitus
Animals
Crystal structure

Keywords

  • PTMs
  • RiPPs
  • dehydration
  • lanthipeptides
  • methyltransferases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

Cite this

Characterization of a Dehydratase and Methyltransferase in the Biosynthesis of Ribosomally Synthesized and Post-translationally Modified Peptides in Lachnospiraceae. / Huo, Liujie; Zhao, Xiling; Acedo, Jeella Z.; Estrada, Paola; Nair, Satish K.; van der Donk, Wilfred A.

In: ChemBioChem, Vol. 21, No. 1-2, 15.01.2020, p. 190-199.

Research output: Contribution to journalArticle

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