Shy Fungi - new drugs : Functional elucidation of unassigned biosynthetic pathways for novel natural products DOI Creative Commons

Olga V. Mosunova

Published: Jan. 1, 2024

The biosynthesis of fungal secondary metabolites: from fundamentals to biotechnological applications Evolution-informed discovery the naphthalenone biosynthetic pathway in fungi Functional elucidation Aspergillus parvulus a novel antibiotic compound melleus

Language: Английский

Enzymatic Insights into the Unusual Formation of Benzolactone and Benzopyran in the Biosynthesis of Spiromarmycin DOI
Yingying Chen,

Linqian Jing,

Ming Peng

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 2809 - 2821

Published: Jan. 31, 2025

Language: Английский

Citations

1
Mechanism Behind the Programmed Biosynthesis of Heterotrimeric Fungal Depside Thielavin A DOI Creative Commons
Qiaolin Ji, Hao Xiang, Wei‐Guang Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(20)

Published: March 12, 2024

Abstract Thielavin A ( 1 ) is a fungal depside composed of one 3‐methylorsellinic acid and two 3,5‐dimethylorsellinic units. It displays diverse biological activities. However, the mechanism underlying assembly heterotrimeric structure remains to be clarified. In this study, we identified polyketide synthase (PKS) involved in biosynthesis . This PKS, designated as ThiA, possesses an unusual domain organization with C ‐methyltransferase (MT) situated at C‐terminus following thioesterase (TE) domain. Our findings indicated that TE solely responsible for rounds ester bond formation, along subsequent chain hydrolysis. We plausible TE‐catalyzed reactions obtained insights into how single PKS can selectively yield specific product. particular, tandem acyl carrier protein domains ThiA are critical programmed methylation by MT Overall, study highlighted occurrence highly optimized domain–domain communication within selective synthesis , which advance our understanding programming rules PKSs.

Language: Английский

Citations

4
Metabolic Blockade-Based Genome Mining of Malbranchea circinata SDU050: Discovery of Diverse Secondary Metabolites DOI Creative Commons
Yang Hu, Xiaowei Luo, Zhuo Shang

et al.

Marine Drugs, Journal Year: 2025, Volume and Issue: 23(1), P. 50 - 50

Published: Jan. 20, 2025

Malbranchea circinata SDU050, a fungus derived from deep-sea sediment, is prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This study reports isolation and identification four classes metabolites wild-type M. alongside five additional metabolite classes, three novel cytochalasins (7–9), obtained mutant strain through metabolic blockade strategy. Furthermore, bioinformatic analysis BGC associated with isocoumarin sclerin (1) enabled deduction its pathway based on function predictions. Bioactivity assays demonstrated that (−)-mycousnine (10) exhibited weak antibacterial activity against Gram-positive bacteria such as Staphylococcus aureus, methicillin-resistant aureus (MRSA), Bacillus subtilis. These findings underscore chemical diversity potential SDU050 highlight an effective strategy for exploring marine fungal

Language: Английский

Citations

0
Genome Mining and Biosynthetic Reconstitution of Fungal Depsidone Mollicellins Reveal a Dual Functional Cytochrome P450 for Ether Formation DOI
Xiaoyang Zhao,

Youzhe Chen,

Ting Yu Long

et al.

Journal of Natural Products, Journal Year: 2023, Volume and Issue: 86(8), P. 2046 - 2053

Published: Aug. 11, 2023

Depsidones are significant in structural diversity and broad biological activities; however, their biosynthetic pathways have not been well understood attracted considerable attention. Herein, we heterologously reconstituted a depsidone encoding gene cluster from Ovatospora sp. SCSIO SY280D Aspergillus nidulans A1145, leading to production of mollicellins, representative family depsidones, discovering bifunctional P450 monooxygenase that catalyzes both ether formation hydroxylation the biosynthesis mollicellins. The functions decarboxylase an aromatic prenyltransferase also characterized understand tailoring modification steps. This work provides important insights into

Language: Английский

Citations

7
Metabologenomics-Inspired Discovery and Combinatorial Biosynthesis-Based Diversification of Fungal O-Glycosylated Depsides DOI
Yang Hu, Zhuo Shang, Yingying Chen

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 20, 2024

Through metabologenomics mining, we prioritized

Language: Английский

Citations

2
Mechanism Behind the Programmed Biosynthesis of Heterotrimeric Fungal Depside Thielavin A DOI Creative Commons
Qiaolin Ji, Hao Xiang, Wei‐Guang Wang

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(20)

Published: March 12, 2024

Abstract Thielavin A ( 1 ) is a fungal depside composed of one 3‐methylorsellinic acid and two 3,5‐dimethylorsellinic units. It displays diverse biological activities. However, the mechanism underlying assembly heterotrimeric structure remains to be clarified. In this study, we identified polyketide synthase (PKS) involved in biosynthesis . This PKS, designated as ThiA, possesses an unusual domain organization with C ‐methyltransferase (MT) situated at C‐terminus following thioesterase (TE) domain. Our findings indicated that TE solely responsible for rounds ester bond formation, along subsequent chain hydrolysis. We plausible TE‐catalyzed reactions obtained insights into how single PKS can selectively yield specific product. particular, tandem acyl carrier protein domains ThiA are critical programmed methylation by MT Overall, study highlighted occurrence highly optimized domain–domain communication within selective synthesis , which advance our understanding programming rules PKSs.

Language: Английский

Citations

1
Novel fungal diphenyl ether biosynthetic gene clusters encode a promiscuous oxidase for elevated antibacterial activities DOI Creative Commons
Qingpei Liu,

Shuaibiao Gao,

Jin Fang

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(35), P. 14248 - 14253

Published: Jan. 1, 2024

Diphenyl ethers (DPEs) are produced by filamentous fungi using polyketide synthases (PKSs) directly, or via Cu oxidase-catalyzed oxidative rearrangements of benzophenone intermediates. Here, we use heterologous expression to reveal a third route towards DPEs in Preussia isomera that relies on an multienzyme cascade convert PKS-generated, ester-linked didepside depsidones and further DPEs, apply comparative genomics identify conserved biosynthetic gene clusters for this pathway multiple fungi. The distribution DPE products is modulated the chassis upon reconstitution. Among post-PKS enzymes, DpeH tyrosinase shows considerable substrate promiscuity synthetic analogues. By creating hybrid enzymes with orthologue from Aspergillus nidulans, C-terminal region alter recognition. Our work highlights evolutionarily way produce provides enzymatic tools generate analogues broad spectrum antibiotic activity against multidrug-resistant human pathogens.

Language: Английский

Citations

1
The aquastatin biosynthetic gene cluster encodes a versatile polyketide synthase capable of synthesising heteromeric depsides with diverse alkyl side chains DOI Creative Commons
Nicolau Sbaraini, Andrew Crombie, John A. Kalaitzis

et al.

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

Published: Jan. 1, 2024

The aqu BGC from Austroacremonium gemini encodes a versatile polyketide synthase capable of synthesising heteromeric depsides with diverse alkyl side chains.

Language: Английский

Citations

1
Recent advances in microbially derived chlorinated antiparasitic compounds DOI

Samriti Saklani,

Sachin S. Chaudhari,

G. N. SHUKLA

et al.

Molecular Diversity, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 30, 2024

Language: Английский

Citations

1
Brominated Depsidones with Antibacterial Effects from a Deep-Sea-Derived Fungus Spiromastix sp. DOI Creative Commons

Zequan Huang,

Dong Liu, Shang Chen

et al.

Marine Drugs, Journal Year: 2024, Volume and Issue: 22(2), P. 78 - 78

Published: Feb. 3, 2024

Eleven new brominated depsidones, namely spiromastixones U-Z5 (

Language: Английский

Citations

0