An ortho‐Quinone Methide Mediates Disulfide Migration in the Biosynthesis of Epidithiodiketopiperazines

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(28)

Published: May 9, 2023

Abstract The transannular disulfide functions as a key structural element imparting diverse biological activities to epidithiodiketopiperazines (ETPs). Although mechanisms were proposed in previous studies, α,β′‐disulfide formation ETPs is not well‐determined owing the failure identify hypothetical intermediate. Herein, we characterize ortho ‐quinone methide ( o ‐QM) intermediate and prove its involvement carbon‐sulfur migration from an α,α′‐ by elucidating pretrichodermamide A biosynthesis, which catalyzed FAD‐dependent thioredoxin oxygenase TdaE harboring noncanonical CXXQ motif. Biochemical investigations of recombinant mutants demonstrated that construction was initiated Gln140 triggering proton abstraction for generation essential ‐QM intermediate, accompanied β′‐acetoxy elimination. Subsequent attack on α,α′‐disulfide Cys137 led spirofuran formation. This study expands biocatalytic toolbox sets stage targeted discovery bioactive ETPs.

Language: Английский

---

Developing filamentous fungal chassis for natural product production

Bioresource Technology, Journal Year: 2024, Volume and Issue: unknown, P. 131703 - 131703

Published: Oct. 1, 2024

Language: Английский

---

Cyclic natural product oligomers: diversity and (bio)synthesis of macrocycles

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 25, 2024

This graphical abstract compares enzymatic and chemical macrocyclization of cyclic natural product oligomers, highlighting bacterial, fungal, plant enzymes, alongside methods like ring-closing metathesis, lactonization, disulfide bridges, cycloaddition.

Language: Английский

---

Vegetation types shape the soil micro-food web compositions and soil multifunctionality in Loess Plateau

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 12, 2025

Introduction Vegetation degradation and soil erosion are severe problems in the Loess hilly region, rendering it one of most ecologically vulnerable areas China globally. restoration has been recognized as an effective approach to amending fragile ecological environment restoring degraded ecosystems. Methods The effects different vegetation types: Caragana korshinskii, Prunus armeniaca L., Pinus tabuliformis Carrière, Medicago sativa control Stipa bungeana on micro-food webs multifunctionality, well their response mechanisms environmental drivers, were investigated using High-throughput sequencing technology. Results C. korshinskii significantly enhanced physicochemical properties enzyme activities by facilitating stability web structure driven bacteria fungi increasing multifunctionality contrast S. . also improved promoting organic carbon alkaline phosphatase activity. However, suboptimal P. M. Soil pH, along with carbon, nitrogen, phosphorus cycling nutrients enzymes, profoundly influences multifunctionality; among these factors, those related cycles identified key influencing factors. Discussion Therefore, a strategy prioritizing dominant type, supplemented , impacts stabilizing hill regions comparable areas.

Language: Английский

---

Bioinformatics assisted construction of the link between biosynthetic gene clusters and secondary metabolites in fungi

Biotechnology Advances, Journal Year: 2025, Volume and Issue: unknown, P. 108547 - 108547

Published: Feb. 1, 2025

Language: Английский

---

Chaetocin, a Natural Inhibitor of Transketolase, Suppresses the Non-Oxidative Pentose Phosphate Pathway and Inhibits the Growth of Drug-Resistant Non-Small Cell Lung Cancer

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 330 - 330

Published: March 11, 2025

Worldwide, lung cancer is the most common cause of cancer-related death, which made worse by development drug resistance during treatment. It urgent to develop new therapeutic methods and small molecule drugs for tumor resistance. Chaetocin, extracted from Chaetomium minutum, a natural compound with good antitumor activity. However, there are few studies on its In this paper, firstly, chaetotocin significantly inhibited viability migration cisplatin-resistant non-small cell (NSCLC) cells xenograft growth nude mice. Chaetocin at 4 mg/kg A549/DDP an inhibition rate 70.43%. Subsequently, underlying mechanism behind actions chaetocin was explored. discovered that can inhibit transketolase (TKT), thereby inhibiting NSCLC inducing death. Compared cisplatin-sensitive cells, lower concentration cisplatin-resistance migration. Mechanistically, TKT identified as potential target chaetocin. The KD value interaction between 63.2 μM. An amount 0.2 μM may suppress enzyme activity expression level TKT. We found higher in further explains why these were more vulnerable terms phenotype. Additionally, muti-omics analysis RNA interference suggested PI3K/Akt signaling pathway through conclusion, could directly bind TKT, expression, interfered intracellular metabolism oxidation-reduction balance, then regulated induce apoptosis.

Language: Английский

---

Novel Epidithiodiketopiperazine Derivatives in the Mutants of the Filamentous Fungus Trichoderma hypoxylon

Journal of Fungi, Journal Year: 2025, Volume and Issue: 11(4), P. 241 - 241

Published: March 22, 2025

Epidithiodiketopiperazines (ETPs) are a class of fungal secondary metabolites (SMs) featuring transannular disulfide bridge at the diketopiperazine (DKP) core. The complex structures and biological activities have attracted widespread attention from biologists chemists. In this study, we identified five novel ETP derivatives 4–7 4′ three gene deletion mutants Trichoderma hypoxylon CGMCC 3.17906, including ΔtdaP, ΔtdaQ, ΔtdaQΔtdaI. Their were characterized through NMR HR-ESI-MS data analysis. Compounds 4 unique heteroatom substitutions α α′ positions, compound 5 possesses α, β′-disulfide bridge, compounds 6 7 contain C3′-(thio)carbonyl group. Based on structural elucidation biosynthetic pathway bridged ETPs, also proposed formation 4′. This study not only expands chemical diversity but offers new mechanistic insights into pathways ETPs.

Language: Английский

---

Functional diversification of epidithiodiketopiperazine methylation and oxidation towards pathogenic fungi

Mycology&#58 An International Journal on Fungal Biology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 14

Published: May 21, 2025

Language: Английский

---

Natural products with 1,2-oxazine scaffold: occurrence, chemical diversity, bioactivity, synthesis, and biosynthesis

Natural Product Reports, Journal Year: 2023, Volume and Issue: 40(12), P. 1874 - 1900

Published: Jan. 1, 2023

This review summarizes the chemical family of natural products with 1,2-oxazine scaffold, focusing on their source organisms, structural diversities, bioactivities, synthesis, and biosynthesis.

Language: Английский

---

Quantitative Characterization of Gene Regulatory Circuits Associated With Fungal Secondary Metabolism to Discover Novel Natural Products

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 28, 2024

Abstract Microbial genetic circuits are vital for regulating gene expression and synthesizing bioactive compounds. However, assessing their strength timing, especially in multicellular fungi, remains challenging. Here, an advanced microfluidic platform is combined with a mathematical model enabling precise characterization of fungal regulatory (GRCs) at the single‐cell level. Utilizing this platform, intensity timing 30 transcription factor‐promoter combinations derived from two representative GRCs, using fungus Aspergillus nidulans determined. As proof concept, selected GRC combination utilized to successfully refactor biosynthetic pathways molecules, precisely control production, activate silenced clusters (BGCs). This study provides insights into microbial regulation highlights potential synthetic biology applications discovery novel natural products.

Language: Английский

---