دورية أكاديمية
Biosynthesis of Tasikamides via Pathway Coupling and Diazonium-Mediated Hydrazone Formation.
| العنوان: | Biosynthesis of Tasikamides via Pathway Coupling and Diazonium-Mediated Hydrazone Formation. |
|---|---|
| المؤلفون: | Ma GL; School of Biological Sciences, Nanyang Technological University, 637551 Singapore., Candra H; School of Biological Sciences, Nanyang Technological University, 637551 Singapore., Pang LM; School of Biological Sciences, Nanyang Technological University, 637551 Singapore., Xiong J; School of Pharmacy, Fudan University, Shanghai 201203, P. R. China., Ding Y; Temasek Life Sciences Laboratory Limited, Research Link, National University of Singapore, 117604 Singapore., Tran HT; School of Biological Sciences, Nanyang Technological University, 637551 Singapore., Low ZJ; School of Biological Sciences, Nanyang Technological University, 637551 Singapore., Ye H; School of Biological Sciences, Nanyang Technological University, 637551 Singapore., Liu M; School of Civil and Environmental Engineering, Nanyang Technological University, 639798 Singapore., Zheng J; School of Civil and Environmental Engineering, Nanyang Technological University, 639798 Singapore., Fang M; School of Civil and Environmental Engineering, Nanyang Technological University, 639798 Singapore., Cao B; School of Civil and Environmental Engineering, Nanyang Technological University, 639798 Singapore.; Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, 637551 Singapore., Liang ZX; School of Biological Sciences, Nanyang Technological University, 637551 Singapore. |
| المصدر: | Journal of the American Chemical Society [J Am Chem Soc] 2022 Feb 02; Vol. 144 (4), pp. 1622-1633. Date of Electronic Publication: 2022 Jan 21. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| 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: | Diazonium Compounds/*chemistry , Hydrazones/*chemistry , Oligopeptides/*biosynthesis, Biosynthetic Pathways/genetics ; Hydrazones/chemical synthesis ; Multigene Family ; Oligopeptides/chemistry ; Peptide Synthases/genetics ; Peptide Synthases/metabolism ; Peptides, Cyclic/biosynthesis ; Peptides, Cyclic/chemistry ; Streptomyces/metabolism |
| مستخلص: | Naturally occurring hydrazones are rare despite the ubiquitous usage of synthetic hydrazones in the preparation of organic compounds and functional materials. In this study, we discovered a family of novel microbial metabolites (tasikamides) that share a unique cyclic pentapeptide scaffold. Surprisingly, tasikamides A-C ( 1 - 3 ) contain a hydrazone group (C═N─N) that joins the cyclic peptide scaffold to an alkyl 5-hydroxylanthranilate (AHA) moiety. We discovered that the biosynthesis of 1 - 3 requires two discrete gene clusters, with one encoding a nonribosomal peptide synthetase (NRPS) pathway for assembling the cyclic peptide scaffold and another encoding the AHA-synthesizing pathway. The AHA gene cluster encodes three ancillary enzymes that catalyze the diazotization of AHA to yield an aryl diazonium species (diazo-AHA). The electrophilic diazo-AHA undergoes nonenzymatic Japp-Klingemann coupling with a β-keto aldehyde-containing cyclic peptide precursor to furnish the hydrazone group and yield 1 - 3 . The studies together unraveled a novel mechanism whereby specialized metabolites are formed by the coupling of two biosynthetic pathways via an unprecedented in vivo Japp-Klingemann reaction. The findings raise the prospect of exploiting the arylamine-diazotizing enzymes (AAD) for the in vivo synthesis of aryl compounds and modification of biological macromolecules. |
| المشرفين على المادة: | 0 (Diazonium Compounds) 0 (Hydrazones) 0 (Oligopeptides) 0 (Peptides, Cyclic) EC 6.3.2.- (Peptide Synthases) EC 6.3.2.- (non-ribosomal peptide synthase) |
| تواريخ الأحداث: | Date Created: 20220121 Date Completed: 20220307 Latest Revision: 20220307 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1021/jacs.1c10369 |
| PMID: | 35060699 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-5126 |
|---|---|
| DOI: | 10.1021/jacs.1c10369 |