While bioinformatic evidence of cobalamin-dependent radical -adenosylmethionine (SAM) enzymes has existed since the naming of the radical SAM superfamily in 2001, none were biochemically characterized until 2011. In the past decade, the field has flourished as methodological advances have facilitated study of the subfamily. Because of the ingenuity and perseverance of researchers in this field, we now have functional, mechanistic, and structural insight into how this class of enzymes harnesses the power of both the cobalamin and radical SAM cofactors to achieve catalysis. All of the early characterized enzymes in this subfamily were methylases, but the activity of these enzymes has recently been expanded beyond methylation. We anticipate that the characterized functions of these enzymes will become both better understood and increasingly diverse with continued study.
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http://dx.doi.org/10.1021/acsbiomedchemau.1c00032 | DOI Listing |
mBio
January 2025
Department of Microbiology, University of Illinois Urbana-Champaign, Champaign, Illinois, USA.
Methyl-coenzyme M reductase (MCR), the key catalyst in the anoxic production and consumption of methane, contains an unusual 2-methylglutamine residue within its active site. data show that a B12-dependent radical SAM (rSAM) enzyme, designated MgmA, is responsible for this post-translational modification (PTM). Here, we show that two different MgmA homologs are able to methylate MCR when expressed in , an organism that does not normally possess this PTM.
View Article and Find Full Text PDFISME Commun
January 2024
BioZone, Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada.
The archaeal class is widely and abundantly distributed in anoxic habitats. Metagenomic studies have suggested that they are mixotrophic, capable of CO fixation and heterotrophic growth, and involved in acetogenesis and lignin degradation. We analyzed 35 metagenome-assembled genomes (MAGs), including the first complete circularized MAG (cMAG) of the Bathy-6 subgroup, from the metagenomes of three full-scale pulp and paper mill anaerobic digesters and three laboratory methanogenic enrichment cultures maintained on pre-treated poplar.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Tianjin University, Phamaceutical Engineering, Weijin Road NO.92, 300072, Tianjin, CHINA.
Fluorine and fluorine-containing functional groups play important roles in drugs and agrochemicals. Recently, SAM-dependent methyltransferases and several SAM analogues have been reported for fluoromethyl transfer through a nucleophilic mechanism. However, fluoromethylation of unactivated carbon centers is very challenging, and their substitution usually involves a radical mechanism.
View Article and Find Full Text PDFACS Bio Med Chem Au
December 2024
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
Cobalamin (Cbl)-dependent radical -adenosylmethionine (SAM) enzymes constitute a large subclass of radical SAM (RS) enzymes that use Cbl to catalyze various types of reactions, the most common of which are methylations. Most Cbl-dependent RS enzymes contain an N-terminal Rossmann fold that aids Cbl binding. Recently, it has been demonstrated that the methanogenesis marker protein 10 (Mmp10) requires Cbl to methylate an arginine residue in the α-subunit of methyl coenzyme M reductase.
View Article and Find Full Text PDFBiochemistry
December 2024
Division of Chemical Biology & Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, United States.
Radical -adenosyl-l-methionine (SAM) enzymes catalyze radical mediated chemical transformations notable for their diversity. The radical mediated reactions that take place in their catalytic cycles can be characterized with respect to one or more phases of initiation, propagation, and termination. Mechanistic models abound regarding these three phases of catalysis being regularly informed and updated by new discoveries that offer insights into their detailed workings.
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