C-Methylation of S-adenosyl-L-Methionine Occurs Prior to Cyclopropanation in the Biosynthesis of 1-Amino-2-Methylcyclopropanecarboxylic Acid (Norcoronamic Acid) in a Bacterium
Open Access
- 15 May 2020
- journal article
- research article
- Published by MDPI AG in Biomolecules
- Vol. 10 (5), 775
- https://doi.org/10.3390/biom10050775
Abstract
Many pharmacologically important peptides are bacterial or fungal in origin and contain nonproteinogenic amino acid (NPA) building blocks. Recently, it was reported that, in bacteria, a cyclopropane-containing NPA 1-aminocyclopropanecarboxylic acid (ACC) is produced from the L-methionine moiety of S-adenosyl-L-methionine (SAM) by non-canonical ACC-forming enzymes. On the other hand, it has been suggested that a monomethylated ACC analogue, 2-methyl-ACC (MeACC), is derived from L-valine. Therefore, we have investigated the MeACC biosynthesis by identifying a gene cluster containing bacterial MeACC synthase genes. In this gene cluster, we identified two genes, orf29 and orf30, which encode a cobalamin (B12)-dependent radical SAM methyltransferase and a bacterial ACC synthase, respectively, and were found to be involved in the MeACC biosynthesis. In vitro analysis using their recombinant enzymes (rOrf29 and rOrf30) further revealed that the ACC structure of MeACC was derived from the L-methionine moiety of SAM, rather than L-valine. In addition, rOrf29 was found to catalyze the C-methylation of the L-methionine moiety of SAM. The resulting methylated derivative of SAM was then converted into MeACC by rOrf30. Thus, we demonstrate that C-methylation of SAM occurs prior to cyclopropanation in the biosynthesis of a bacterial MeACC (norcoronamic acid).Keywords
Funding Information
- Japan Society for the Promotion of Science (16H06451, 16H06445, 18H02095, 19K05776, A3 foresight program)
This publication has 32 references indexed in Scilit:
- Biosynthetic Pathways to Nonproteinogenic α-Amino AcidsChemical Reviews, 2019
- Structural basis of the nonribosomal codes for nonproteinogenic amino acid selective adenylation enzymes in the biosynthesis of natural productsJournal of Industrial Microbiology & Biotechnology, 2018
- Colibactin assembly line enzymes use S-adenosylmethionine to build a cyclopropane ringNature Chemical Biology, 2017
- Nonproteinogenic Amino Acid Building Blocks for Nonribosomal Peptide and Hybrid Polyketide ScaffoldsAngewandte Chemie-International Edition, 2013
- Enzymatic Chemistry of Cyclopropane, Epoxide, and Aziridine BiosynthesisChemical Reviews, 2011
- Biosynthesis and Metabolism of Cyclopropane Rings in Natural CompoundsChemical Reviews, 2003
- Nonribosomal peptides: from genes to productsNatural Product Reports, 2003
- Ways of Assembling Complex Natural Products on Modular Nonribosomal Peptide Synthetases A list of abbreviations can be found at the end of the text.ChemBioChem, 2002
- Modular Peptide Synthetases Involved in Nonribosomal Peptide SynthesisChemical Reviews, 1997
- Ethylene biosynthesis: Identification of 1-aminocyclopropane-1-carboxylic acid as an intermediate in the conversion of methionine to ethyleneProceedings of the National Academy of Sciences of the United States of America, 1979