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Arsinothricin Biosynthesis Involving a Radical SAM Enzyme for Noncanonical SAM Cleavage and C-As Bond Formation.

التفاصيل البيبلوغرافية
العنوان: Arsinothricin Biosynthesis Involving a Radical SAM Enzyme for Noncanonical SAM Cleavage and C-As Bond Formation.
المؤلفون: Yao Y; Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China., He J; Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China., Chen F; Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China., Dong M; Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.; Haihe Laboratory of Sustainable Chemical Transformations, Tianjin 300192, China.
المصدر: Journal of the American Chemical Society [J Am Chem Soc] 2024 Aug 07; Vol. 146 (31), pp. 21214-21219. Date of Electronic Publication: 2024 Jul 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 7503056 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5126 (Electronic) Linking ISSN: 00027863 NLM ISO Abbreviation: J Am Chem Soc Subsets: MEDLINE
أسماء مطبوعة: Publication: Washington, DC : American Chemical Society
Original Publication: Easton, Pa. [etc.]
مواضيع طبية MeSH: S-Adenosylmethionine*/metabolism , S-Adenosylmethionine*/chemistry, Arsenic/metabolism ; Arsenic/chemistry ; Bacterial Proteins/metabolism ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics
مستخلص: Arsinothricin is a potent antibiotic secreted by soil bacteria. The biosynthesis of arsinothricin was proposed to involve a C-As bond formation between trivalent As and the 3-amino-3-carboxypropyl (ACP) group of S -adenosyl-l-methionine (SAM), which is catalyzed by the protein ArsL. However, ArsL has not been characterized in detail. Interestingly, ArsL contains a CxxxCxxC motif and thus belongs to the radical SAM enzyme superfamily, the members of which cleave SAM and generate a 5'-deoxyadenosyl radical. Here, we found that ArsL cleaves the C γ,Met -S bond of SAM and generates an ACP radical that resembles Dph2, a noncanonical radical SAM enzyme involved in diphthamid biosynthesis. As Dph2 does not contain the CxxxCxxC motif, ArsL is a unique radical SAM enzyme that contains this motif but generates a noncanonical ACP radical. Together with the methyltransferase ArsM, we successfully reconstituted arsinothricin biosynthesis in vitro. ArsL has a conserved RCCLKC motif in the C-terminal sequence and belongs to the RCCLKC-tail radical SAM protein subfamily. By truncation and mutagenesis, we showed that this motif plays an important role in binding to the substrate arsenite and is highly important for its activity. Our results suggested that ArsL has a canonical radical SAM enzyme motif but catalyzes a noncanonical radical SAM reaction, implying that more noncanonical radical SAM chemistry may exist within the radical SAM enzyme superfamily.
المشرفين على المادة: 7LP2MPO46S (S-Adenosylmethionine)
N712M78A8G (Arsenic)
0 (Bacterial Proteins)
تواريخ الأحداث: Date Created: 20240725 Date Completed: 20240807 Latest Revision: 20240916
رمز التحديث: 20240916
DOI: 10.1021/jacs.4c06403
PMID: 39052934
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-5126
DOI:10.1021/jacs.4c06403