Mechanism of S-Adenosyl-l-methionine C-Methylation by Cobalamin-dependent Radical S-Adenosyl-l-methionine Methylase in 1-Amino-2-methylcyclopropanecarboxylic Acid Biosynthesis

Fumitaka Kudo; Atsushi Minato; Shusuke Sato; Nayuta Nagano; Chitose Maruyama; Yoshimitsu Hamano; Junko Hashimoto; Ikuko Kozone; Kazuo Shin-Ya; Tadashi Eguchi

doi:10.1021/acs.orglett.2c03555

Mechanism of S-Adenosyl-l-methionine C-Methylation by Cobalamin-dependent Radical S-Adenosyl-l-methionine Methylase in 1-Amino-2-methylcyclopropanecarboxylic Acid Biosynthesis

Org Lett. 2022 Dec 16;24(49):8975-8979. doi: 10.1021/acs.orglett.2c03555. Epub 2022 Dec 2.

Authors

Affiliations

¹ Department of Chemistry, Tokyo Institute of Technology, O-okayama, Tokyo 152-8551, Japan.
² Department of Bioscience, Fukui Prefectural University, 4-1-1 Yoshida-Gun, Fukui 910-1195, Japan.
³ Japan Biological Informatics Consortium (JBIC), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
⁴ National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.

PMID: 36458844
DOI: 10.1021/acs.orglett.2c03555

Abstract

The radical S-adenosyl-l-methionine (SAM) methylase Orf29 catalyzes the C-methylation of SAM in the biosynthesis of 1-amino-2-methylcyclopropanecarboxylic acid. Here, we determined that the methylation product is (4″R)-4″-methyl-SAM. Furthermore, we found that the 5'-deoxyadenosyl radical generated by Orf29 abstracts the pro-R hydrogen atom from the C-4″ position of SAM to generate the radical intermediate, which reacts with methylcobalamin to give (4″R)-4″-methyl-SAM. Consequently, the Orf29-catalyzed C-methylation was confirmed to proceed with retention of configuration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Methionine*
Methylation
Methyltransferases / metabolism
Racemethionine
S-Adenosylmethionine* / metabolism
Vitamin B 12

Substances

Methionine
Methyltransferases
Racemethionine
S-Adenosylmethionine
Vitamin B 12
1-amino-2-methylcyclopentanecarboxylic acid