New insights into exploring new functional enzymes through the enzyme promiscuity

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 304, P. 140576 - 140576

Published: Feb. 2, 2025

Language: Английский

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Exquisite Complex Reaction Cascade in the Natural 1,2,4-Triazine Assembly

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 29, 2025

1,2,4-Triazine ring is a scaffold widely found in biologically active compounds, but how nature makes it remains enigmatic. In this study, we unveil the complex enzymatic and nonenzymatic cascade reactions that assemble 1,2,4-triazine moiety structures of natural products pseudoiodinine toxoflavin. Through biochemical studies, isotope labeling, application substrate analogues, propose plausible pathway for assembly from common precursor riboflavin biosynthesis. This process involves four two-electron oxidation steps, C-N bond formation, decarboxylation, N-N forming step catalyzed by metal-dependent WD40-repeat (WDR) protein. study thus not only provides first biocatalytic route also identifies previously unrecognized catalytic role large WDR protein family.

Language: Английский

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Discovery, Herbicidal Activity and Biosynthesis of a Novel Natural Tetramic Acid from Alternaria Species

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Abstract The tetramic acid moiety is a pivotal structural unit in numerous natural products. As an analogue of the simplest compound tenuazonic (TeA), sec‐pentyl‐TeA (S‐TeA) exhibits double herbicidal activity TeA. Here, this work identifies S‐TeA as novel product synthesized by Alternaria alternata and three other filamentous fungi. Chiral analysis confirm absolute configuration (5 S , 6 ). Configuration‐bioactivity studies reveal that )‐S‐TeA eutomer possesses highest among all tested diastereomers. Biosynthetic analyses demonstrate threonine precursor to S‐TeA, beginning with production 2‐amino‐3‐methylhexanoic (AMHA) via eight enzymes from branched‐chain amino (BCAA) biosynthetic pathway, including deaminase, 2‐isopropylmalate synthase (IPMS), 3‐isopropylmalate dehydratase (IPMDH), isopropylmalate dehydrogenase (ISMD), acetolactate synthase, ketol‐acid reductoisomerase, dihydroxy dehydratase, BCAA aminotransferase. Subsequently, AMHA undergoes acetylation cyclization non‐ribosomal peptide synthetases form S‐TeA. Distinct differences pathways TeA are identified. In vitro critical roles unique IPMS, IPMDH, ISMD biosynthesis, which absent biosynthesis. These findings provide solid basis for developing herbicide.

Language: Английский

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Characterization of the Flavin-Dependent Monooxygenase Involved in the Biosynthesis of the Nocardiosis-Associated Polyketide

Biochemistry, Journal Year: 2024, Volume and Issue: 63(21), P. 2868 - 2877

Published: Oct. 21, 2024

Some species of the

Language: Английский

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Recent Developments and Challenges in the Enzymatic Formation of Nitrogen–Nitrogen Bonds

ACS Catalysis, Journal Year: 2024, Volume and Issue: 15(1), P. 310 - 342

Published: Dec. 17, 2024

The biological formation of nitrogen–nitrogen (N–N) bonds represents intriguing reactions that have attracted much attention in the past decade. This interest has led to an increasing number N–N bond-containing natural products (NPs) and related enzymes catalyze their (referred this review as NNzymes) being elucidated studied greater detail. While more detailed information on biosynthesis NPs, which only become available recent years, provides unprecedented source biosynthetic enzymes, potential for biocatalytic applications been minimally explored. With review, we aim not provide a comprehensive overview both characterized NNzymes hypothetical biocatalysts with putative bond forming activity, but also highlight from perspective. We present compare conventional synthetic approaches linear cyclic hydrazines, hydrazides, diazo- nitroso-groups, triazenes, triazoles allow comparison enzymatic routes via these functional groups. Moreover, pathways well diversity reaction mechanisms are presented according direct groups currently accessible enzymes.

Language: Английский

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Catalysis-enabled amine sorting

Nature Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Language: Английский

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Enzymatic azide synthesis by ATP-dependent synthetase

Chem Catalysis, Journal Year: 2024, Volume and Issue: 4(12), P. 101226 - 101226

Published: Dec. 1, 2024

Language: Английский

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