Harzianolides B–G: Undescribed Butenolides isolated from the fungus Trichoderma harzianum ZN-4

Fitoterapia, Journal Year: 2024, Volume and Issue: 176, P. 106039 - 106039

Published: May 25, 2024

Language: Английский

Targeted discovery of polyketides with antioxidant activity through integrated omics and cocultivation strategies

Applied and Environmental Microbiology, Journal Year: 2024, Volume and Issue: 90(11)

Published: Nov. 1, 2024

ABSTRACT Fungi generate a diverse array of bioactive compounds with significant pharmaceutical applications. However, the chemical diversity natural products in fungi remains largely unexplored. Here, we present paradigm for specifically discovering and from by integrating genome mining building block molecular network coculture analysis. Through pangenome sequence similarity analysis, identified rare type I polyketide enzyme Penicillium sp. ZJUT-34. Subsequent strategy led to identification isolation pair novel polyketides, (±)-peniphenone E [(±)− 1 ], three known polyketides ( 2–4 ), precursor 5–7 ) combined culture ZJUT-34 ZJUT23. Their structures were established through extensive spectroscopic including NMR HRESIMS. Chiral HPLC separation compound yielded enantiomers (+)− (−)− , their absolute configurations determined using calculated ECD methods. Compound (±)− is notable its unprecedented structure, featuring unique 2-methyl-hexenyl-3-one moiety fused clavatol core. We proposed hypothetical biosynthetic pathway . Furthermore, 2 5 6 exhibited strong antioxidant activity, whereas 3 four moderate activity compared positive control, ascorbic acid. Our research demonstrates pioneering uncovering merging mining, metabolomics, cocultivation This approach addresses challenge produced enzymes that are often silent under conventional conditions due gene regulation. IMPORTANCE Polyketides, particularly those complex structures, crucial drug development synthesis. study introduces discover new genomics, strategies. By combining networks, coculturing techniques, isolated polyketide, E, along highlights potential strategies explore fungal compounds. The successful distinctive effectiveness this integrated method enhancing product discovery underscores value innovative approaches research.

Language: Английский

MolBiC: the cell-based landscape illustrating molecular bioactivities

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 53(D1), P. D1683 - D1691

Published: Oct. 7, 2024

The measurement of cell-based molecular bioactivity (CMB) is critical for almost every step drug development. With the booming application AI in biomedicine, it essential to have CMB data promote learning patterns guiding modern discovery, but no database providing such information has been constructed yet. In this study, we introduce MolBiC, a knowledge base designed describe valuable on measured within cellular context. MolBiC features 550 093 experimentally validated CMBs, encompassing 321 086 molecules and 2666 targets across 988 cell lines. Our unique describing CMB, which meets demands CMB-based big promoting molecular/pharmaceutical pattern discovery now freely accessible without any login requirement at: https://idrblab.org/MolBiC/.

Language: Английский