524-70-9Relevant articles and documents
S-Adenosyl-l-ethionine is a Catalytically Competent Analog of S-Adenosyl-l-methionine (SAM) in the Radical SAM Enzyme HydG
Impano, Stella,Yang, Hao,Shepard, Eric M.,Swimley, Ryan,Pagnier, Adrien,Broderick, William E.,Hoffman, Brian M.,Broderick, Joan B.
supporting information, p. 4666 - 4672 (2021/01/20)
Radical S-adenosyl-l-methionine (SAM) enzymes initiate biological radical reactions with the 5′-deoxyadenosyl radical (5′-dAdo.). A [4Fe-4S]+ cluster reductively cleaves SAM to form the Ω organometallic intermediate in which the 5′-deoxyadenosyl moiety is directly bound to the unique iron of the [4Fe-4S] cluster, with subsequent liberation of 5′-dAdo.. We present synthesis of the SAM analog S-adenosyl-l-ethionine (SAE) and show SAE is a mechanistically equivalent SAM-alternative for HydG, both supporting enzymatic turnover of substrate tyrosine and forming the organometallic intermediate Ω. Photolysis of SAE-bound HydG forms an ethyl radical trapped in the active site. The ethyl radical withstands prolonged storage at 77 K and its EPR signal is only partially lost upon annealing at 100 K, making it significantly less reactive than the methyl radical formed by SAM photolysis. Upon annealing above 77 K, the ethyl radical adds to the [4Fe-4S]2+ cluster, generating an ethyl-[4Fe-4S]3+ organometallic species termed ΩE.
Facile chemoenzymatic strategies for the synthesis and utilization of S-adenosyl-L-methionine analogues
Singh, Shanteri,Zhang, Jianjun,Huber, Tyler D.,Sunkara, Manjula,Hurley, Katherine,Goff, Randal D.,Wang, Guojun,Zhang, Wen,Liu, Chunming,Rohr, Juergen,Van Lanen, Steven G.,Morris, Andrew J.,Thorson, Jon S.
supporting information, p. 3965 - 3969 (2014/05/06)
A chemoenzymatic platform for the synthesis of S-adenosyl-L-methionine (SAM) analogues compatible with downstream SAM-utilizing enzymes is reported. Forty-four non-native S/Se-alkylated Met analogues were synthesized and applied to probing the substrate specificity of five diverse methionine adenosyltransferases (MATs). Human MAT II was among the most permissive of the MATs analyzed and enabled the chemoenzymatic synthesis of 29 non-native SAM analogues. As a proof of concept for the feasibility of natural product alkylrandomization , a small set of differentially-alkylated indolocarbazole analogues was generated by using a coupled hMAT2-RebM system (RebM is the sugar C4′-O-methyltransferase that is involved in rebeccamycin biosynthesis). The ability to couple SAM synthesis and utilization in a single vessel circumvents issues associated with the rapid decomposition of SAM analogues and thereby opens the door for the further interrogation of a wide range of SAM utilizing enzymes. Mix and MATch: Methionine adenosyltransferase (MAT) was used to synthesize S-adenosylmethionine (SAM) analogues in a method directly compatible with downstream SAM-utilizing enzymes. As a proof of concept for the feasibility of natural product alkylrandomization by using this method, a coupled strategy in which MAT was applied in conjunction with the methyltransferase RebM was used to generate a small set of indolocarbazole analogues.
