{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bengel LL"],"funding":["Bundesministerium für Bildung und Forschung","Deutsche Forschungsgemeinschaft"],"pagination":["5554-5560"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7986378"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["60(10)"],"pubmed_abstract":["Selective alkylation of pyrazoles could solve a challenge in chemistry and streamline synthesis of important molecules. Here we report catalyst-controlled pyrazole alkylation by a cyclic two-enzyme cascade. In this enzymatic system, a promiscuous enzyme uses haloalkanes as precursors to generate non-natural analogs of the common cosubstrate S-adenosyl-l-methionine. A second engineered enzyme transfers the alkyl group in highly selective C-N bond formations to the pyrazole substrate. The cosubstrate is recycled and only used in catalytic amounts. Key is a computational enzyme-library design tool that converted a promiscuous methyltransferase into a small enzyme family of pyrazole-alkylating enzymes in one round of mutagenesis and screening. With this enzymatic system, pyrazole alkylation (m"],"journal":["Angewandte Chemie (International ed. in English)"],"pubmed_title":["Engineered Enzymes Enable Selective N-Alkylation of Pyrazoles With Simple Haloalkanes."],"pmcid":["PMC7986378"],"funding_grant_id":["420112577","031B0359A"],"pubmed_authors":["Bengel LL","Kienzle S","Hammer SC","Aberle B","Hauer B","Egler-Kemmerer AN"],"additional_accession":[]},"is_claimable":false,"name":"Engineered Enzymes Enable Selective N-Alkylation of Pyrazoles With Simple Haloalkanes.","description":"Selective alkylation of pyrazoles could solve a challenge in chemistry and streamline synthesis of important molecules. Here we report catalyst-controlled pyrazole alkylation by a cyclic two-enzyme cascade. In this enzymatic system, a promiscuous enzyme uses haloalkanes as precursors to generate non-natural analogs of the common cosubstrate S-adenosyl-l-methionine. A second engineered enzyme transfers the alkyl group in highly selective C-N bond formations to the pyrazole substrate. The cosubstrate is recycled and only used in catalytic amounts. Key is a computational enzyme-library design tool that converted a promiscuous methyltransferase into a small enzyme family of pyrazole-alkylating enzymes in one round of mutagenesis and screening. With this enzymatic system, pyrazole alkylation (m","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2025-04-05T15:25:50.317Z","creation":"2025-04-05T15:25:50.317Z"},"accession":"S-EPMC7986378","cross_references":{"pubmed":["33300646"],"doi":["10.1002/anie.202014239"]}}