دورية أكاديمية
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Efficient Transferase Engineering for SAM Analog Synthesis from Iodoalkanes.

التفاصيل البيبلوغرافية
العنوان: Efficient Transferase Engineering for SAM Analog Synthesis from Iodoalkanes.
المؤلفون: Schülke KH; Organic Chemistry and Biocatalysis, Faculty of Chemistry, Bielefeld University, Universitätsstraße 25, 33615, Bielefeld, Germany., Fröse JS; Organic Chemistry and Biocatalysis, Faculty of Chemistry, Bielefeld University, Universitätsstraße 25, 33615, Bielefeld, Germany., Klein A; Organic Chemistry and Biocatalysis, Faculty of Chemistry, Bielefeld University, Universitätsstraße 25, 33615, Bielefeld, Germany., Garcia-Borràs M; Department Institut de Química Computacional i Catàlisi (IQCC), Departament de Química, Universitat de Girona, 17003, Girona, Catalonia, Spain., Hammer SC; Organic Chemistry and Biocatalysis, Faculty of Chemistry, Bielefeld University, Universitätsstraße 25, 33615, Bielefeld, Germany.
المصدر: Chembiochem : a European journal of chemical biology [Chembiochem] 2024 May 17; Vol. 25 (10), pp. e202400079. Date of Electronic Publication: 2024 Apr 15.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley-VCH Verlag Country of Publication: Germany NLM ID: 100937360 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1439-7633 (Electronic) Linking ISSN: 14394227 NLM ISO Abbreviation: Chembiochem Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Weinheim, Germany : Wiley-VCH Verlag, c2000-
مواضيع طبية MeSH: S-Adenosylmethionine*/metabolism , S-Adenosylmethionine*/chemistry , Protein Engineering*, Alkylation ; Hydrocarbons, Iodinated/chemistry ; Biocatalysis ; Molecular Structure
مستخلص: S-Adenosyl-l-methionine (SAM) is an important cosubstrate in various biochemical processes, including selective methyl transfer reactions. Simple methods for the (re)generation of SAM analogs could expand the chemistry accessible with SAM-dependent transferases and go beyond methylation reactions. Here we present an efficient enzyme engineering strategy to synthesize different SAM analogs from "off-the-shelf" iodoalkanes through enzymatic alkylation of S-adenosyl-l-homocysteine (SAH). This was achieved by mutating multiple hydrophobic and structurally dynamic amino acids simultaneously. Combinatorial mutagenesis was guided by the natural amino acid diversity and generated a highly functional mutant library. This approach increased the speed as well as the scale of enzyme engineering by providing a panel of optimized enzymes with orders of magnitude higher activities for multiple substrates in just one round of enzyme engineering. The optimized enzymes exhibit catalytic efficiencies up to 31 M -1  s -1 , convert various iodoalkanes, including substrates bearing cyclopropyl or aromatic moieties, and catalyze S-alkylation of SAH with very high stereoselectivities (>99 % de). We further report a high throughput chromatographic screening system for reliable and rapid SAM analog analysis. We believe that the methods and enzymes described herein will further advance the field of selective biocatalytic alkylation chemistry by enabling SAM analog regeneration with "off-the-shelf" reagents.
(© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)
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معلومات مُعتمدة: 420112577 Deutsche Forschungsgemeinschaft (DFG); 510974120 DFG; 20020/690 Deutsche Bundesstiftung Umwelt; PID2022-141676NB-I00 Spanish Ministerio de Ciencia e Innovación; RYC2020-028628-I Spanish Ministerio de Ciencia e Innovación; 495518010 Deutsche Forschungsgemeinschaft
فهرسة مساهمة: Keywords: Biocatalysis; Enzyme engineering; Methyltransferases; SAM analogs
تواريخ الأحداث: Date Created: 20240313 Date Completed: 20240517 Latest Revision: 20240517
رمز التحديث: 20240517
DOI: 10.1002/cbic.202400079
PMID: 38477872
قاعدة البيانات: MEDLINE
الوصف
تدمد:1439-7633
DOI:10.1002/cbic.202400079