Radical S-Adenosylmethionine (SAM) Enzymes in Cofactor Biosynthesis: A Treasure Trove of Complex Organic Radical Rearrangement Reactions*

In this minireview, we describe the radical S-adenosylmethionine enzymes involved in the biosynthesis of thiamin, menaquinone, molybdopterin, coenzyme F420, and heme. Our focus is on the remarkably complex organic rearrangements involved, many of which have no precedent in organic or biological chemistry.

[1]  J. Jarrett.  The Biosynthesis of Thiol- and Thioether-containing Cofactors and Secondary Metabolites Catalyzed by Radical S-Adenosylmethionine Enzymes* , 2014, The Journal of Biological Chemistry.

[2]  P. Amara,et al.  Crystal structure of tryptophan lyase (NosL): evidence for radical formation at the amino group of tryptophan. , 2014, Angewandte Chemie.

[3]  W. Myers,et al.  Paramagnetic Intermediates Generated by Radical S-Adenosylmethionine (SAM) Enzymes , 2014, Accounts of chemical research.

[4]  T. Begley,et al.  Molybdopterin Biosynthesis: Trapping of Intermediates for the MoaA-Catalyzed Reaction Using 2′-DeoxyGTP and 2′-ChloroGTP as Substrate Analogues. , 2014, Journal of the American Chemical Society.

[5]  J. Broderick,et al.  Radical S-Adenosylmethionine Enzymes , 2014, Chemical reviews.

[6]  W. Myers,et al.  The HydG Enzyme Generates an Fe(CO)2(CN) Synthon in Assembly of the FeFe Hydrogenase H-Cluster , 2014, Science.

[7]  T. Begley,et al.  Menaquinone biosynthesis: formation of aminofutalosine requires a unique radical SAM enzyme. , 2013, Journal of the American Chemical Society.

[8]  T. Begley,et al.  Molybdopterin biosynthesis: trapping an unusual purine ribose adduct in the MoaA-catalyzed reaction. , 2013, Journal of the American Chemical Society.

[9]  In vitro reconstitution of the radical S-adenosylmethionine enzyme MqnC involved in the biosynthesis of futalosine-derived menaquinone. , 2013, Biochemistry.

[10]  K. Yokoyama,et al.  Identification of a cyclic nucleotide as a cryptic intermediate in molybdenum cofactor biosynthesis. , 2013, Journal of the American Chemical Society.

[11]  T. Begley,et al.  Catalysis of a new ribose carbon-insertion reaction by the molybdenum cofactor biosynthetic enzyme MoaA. , 2013, Biochemistry.

[12]  Robert L. White,et al.  Biosynthesis of F0, precursor of the F420 cofactor, requires a unique two radical-SAM domain enzyme and tyrosine as substrate. , 2012, Journal of the American Chemical Society.

[13]  T. Dairi.  Menaquinone biosyntheses in microorganisms. , 2012, Methods in enzymology.

[14]  Isao Fujii,et al.  Convergent Strategies in Biosynthesis , 2011 .

[15]  J. Freed,et al.  Diphthamide biosynthesis requires an organic radical generated by an iron–sulphur enzyme , 2011, Nature.

[16]  K. Rajagopalan,et al.  The History of the Discovery of the Molybdenum Cofactor and Novel Aspects of its Biosynthesis in Bacteria. , 2011, Coordination chemistry reviews.

[17]  P. Roach.  Radicals from S-adenosylmethionine and their application to biosynthesis. , 2011, Current opinion in chemical biology.

[18]  C. Drennan,et al.  Structural insights into radical generation by the radical SAM superfamily. , 2011, Chemical reviews.

[19]  I. Alabugin,et al.  Radical O→C transposition: a metal-free process for conversion of phenols into benzoates and benzamides. , 2011, The Journal of organic chemistry.

[20]  B. Shen,et al.  Radical-Mediated Enzymatic Carbon Chain Fragmentation-Recombination , 2010, Nature chemical biology.

[21]  Tadhg P Begley,et al.  A "radical dance" in thiamin biosynthesis: mechanistic analysis of the bacterial hydroxymethylpyrimidine phosphate synthase. , 2010, Angewandte Chemie.

[22]  I. Alabugin,et al.  Metal-free transformation of phenols into substituted benzamides: a highly selective radical 1,2-O→C transposition in O-aryl-N-phenylthiocarbamates. , 2010, Chemistry.

[23]  D. Cicero,et al.  The O-neophyl rearrangement of 1,1-diarylalkoxyl radicals. Experimental evidence for the formation of an intermediate 1-oxaspiro(2,5)octadienyl radical , 2010 .

[24]  P. Roach,et al.  Catalytic Activity of the Anaerobic Tyrosine Lyase Required for Thiamine Biosynthesis in Escherichia coli* , 2009, The Journal of Biological Chemistry.

[25]  H. Schindelin,et al.  ENDOR spectroscopy shows that guanine N1 binds to [4Fe-4S] cluster II of the S-adenosylmethionine-dependent enzyme MoaA: mechanistic implications. , 2009, Journal of the American Chemical Society.

[26]  C. Krebs,et al.  Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily. , 2008, Nature chemical biology.

[27]  Jun Ishikawa,et al.  An Alternative Menaquinone Biosynthetic Pathway Operating in Microorganisms , 2008, Science.

[28]  T. Dairi,et al.  Studies on a new biosynthetic pathway for menaquinone. , 2008, Journal of the American Chemical Society.

[29]  Adrian D Hegeman,et al.  The Radical SAM Superfamily. , 2008, Critical reviews in biochemistry and molecular biology.

[30]  P. Roach,et al.  Thiamine biosynthesis in Escherichia coli: identification of the intermediate and by-product derived from tyrosine. , 2007, Angewandte Chemie.

[31]  D. Jahn,et al.  The Substrate Radical of Escherichia coli Oxygen-independent Coproporphyrinogen III Oxidase HemN* , 2006, Journal of Biological Chemistry.

[32]  H. Schindelin,et al.  Binding of 5'-GTP to the C-terminal FeS cluster of the radical S-adenosylmethionine enzyme MoaA provides insights into its mechanism. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[33]  D. Jahn,et al.  Structural and functional comparison of HemN to other radical SAM enzymes , 2005, Biological chemistry.

[34]  R. Mehl,et al.  Biosynthesis of the thiamin pyrimidine: the reconstitution of a remarkable rearrangement reaction. , 2004, Organic & biomolecular chemistry.

[35]  D. Jahn,et al.  Crystal structure of coproporphyrinogen III oxidase reveals cofactor geometry of Radical SAM enzymes , 2003, The EMBO journal.

[36]  Jorge F. Reyes-Spindola,et al.  Radical SAM, a novel protein superfamily linking unresolved steps in familiar biosynthetic pathways with radical mechanisms: functional characterization using new analysis and information visualization methods. , 2001, Nucleic acids research.

[37]  K. Yamada,et al.  The origin of the nitrogen atoms of the pyrimidine moiety of thiamin under anaerobic conditions in Escherichia coli , 1999 .

[38]  W. Eisenreich,et al.  Rearrangement reactions in the biosynthesis of molybdopterin , 1998 .

[39]  J. Atkinson,et al.  Cytochrome P450 hydroxylation of hydrocarbons: variation in the rate of oxygen rebound using cyclopropyl radical clocks including two new ultrafast probes. , 1993, Biochemistry.

[40]  J. Seehra,et al.  Anaerobic and aerobic coproporphyrinogen III oxidases of Rhodopseudomonas spheroides. Mechanism and stereochemistry of vinyl group formation. , 1983, The Biochemical journal.

[41]  K. Yamada.  Biosynthesis of thiamin. Incorporation of a two-carbon fragment derived from ribose of 5-aminoimidazole ribotide into the pyrimidine moiety of thiamin , 1982 .