Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/155779
Title: Biosynthesis of tasikamides via pathway coupling and diazonium-mediated hydrazone formation
Authors: Ma, Guang-Lei
Candra, Hartono
Pang, Li Mei
Xiong, Juan
Ding, Yichen
Tran, Hoa Thi
Low, Zhen Jie
Ye, Hong
Liu, Min
Zheng, Jie
Fang, Mingliang
Cao, Bin
Liang, Zhao-Xun
Keywords: Science::Biological sciences::Microbiology
Issue Date: 2022
Source: Ma, G., Candra, H., Pang, L. M., Xiong, J., Ding, Y., Tran, H. T., Low, Z. J., Ye, H., Liu, M., Zheng, J., Fang, M., Cao, B. & Liang, Z. (2022). Biosynthesis of tasikamides via pathway coupling and diazonium-mediated hydrazone formation. Journal of the American Chemical Society, 144(4), 1622-1633. https://dx.doi.org/10.1021/jacs.1c10369
Project: NIM/03/2017 
NRF-SBP-01 
Journal: Journal of the American Chemical Society 
Abstract: 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.
URI: https://hdl.handle.net/10356/155779
ISSN: 0002-7863
DOI: 10.1021/jacs.1c10369
Schools: School of Biological Sciences 
School of Civil and Environmental Engineering 
Research Centres: Singapore Centre for Environmental Life Sciences and Engineering (SCELSE) 
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/jacs.1c10369.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:CEE Journal Articles
SBS Journal Articles
SCELSE Journal Articles

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