Over the past 10 years, considerable progress has been made in our understanding of the mechanistic enzymology of the Radical-SAM enzymes. It is now clear that these enzymes appear to be involved in a remarkably wide range of chemically challenging reactions. This review article highlights mechanistic and structural aspects of the methylthiotransferases (MTTases) sub-class of the Radical-SAM enzymes. The mechanism of methylthio insertion, now observed to be performed by three different enzymes is an exciting unsolved problem. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.
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http://dx.doi.org/10.1016/j.bbapap.2011.11.007 | 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 PDFAngew Chem Int Ed Engl
December 2024
Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, 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.
View Article and Find Full Text PDFJ Am Chem Soc
November 2024
Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina 27710, United States.
Dynobactins are recently discovered ribosomally synthesized and post-translationally modified peptide (RiPP) antibiotics that selectively kill Gram-negative pathogens by inhibiting the β-barrel assembly machinery (Bam) located on their outer membranes. Such activity of dynobactins derives from their unique cross-links between Trp1-Asn4 and His6-Tyr8. In particular, the His6-Tyr8 cross-link is formed between N of His6 and C of Tyr8, an unprecedented type of cross-link in RiPP natural products.
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