Comparative Genomic Analysis Reveals Key Changes in the Genome of Acremonium chrysogenum That Occurred During Classical Strain Improvement for Production of Antibiotic Cephalosporin C DOI Open Access
Alexander A. Zhgun

International Journal of Molecular Sciences, Год журнала: 2024, Номер 26(1), С. 181 - 181

Опубликована: Дек. 28, 2024

From the 1950s to present, main tool for obtaining fungal industrial producers of secondary metabolites remains so-called classical strain improvement (CSI) methods associated with multi-round random mutagenesis and screening level target products. As a result application such techniques, yield in high-yielding (HY) strains was increased hundreds times compared wild-type (WT) parental strains. However, events that occur at molecular during CSI programs are still unknown. In this paper, an attempt made identify characteristic changes genome occurred

Язык: Английский

Structural and Mechanistic Characterization of the Flavin-Dependent Monooxygenase and Oxidase Involved in Sorbicillinoid Biosynthesis DOI Creative Commons
Gwen Tjallinks,

Nicolò Angeleri,

Quoc‐Thai Nguyen

и другие.

ACS Chemical Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

Sorbicillinoids are yellow secondary metabolites synthesized through an elegant combination of enzymatic and spontaneous biochemical processes. The flavin-dependent monooxygenase SorC oxidase SorD crucial in this interplay, enabling the generation a diverse array functionally complex sorbicillinoids. By solving crystal structures from Penicillium chrysogenum with sorbicillin bound active site, we describe catalytically binding conformations, for attaining enantioselective stereoselective control these reactions. structure was resolved cofactor FAD its out state, which allowed us to identify key residues that modulate flavin mobility other conformational changes. Catalytic were also confirmed by detailed characterization wild-type several variants. Meanwhile, using CRISPR/Cas9-based multicopy-genome integration system, could heterologously express P. Aspergillus niger high yields purity. This obtain viable catalytic conformation. Structural analysis obtained provided insights into substrate pose highlighted potentially critical site residues. Ultimately, having both at our disposal enabled investigate their functions interplays biosynthesis vast

Язык: Английский

Процитировано

0

Trichodenoids A and B, Two Skeletally Unprecedented Polyketides from Trichoderma reesei with Cardioprotective Effects against H2O2-Induced Injury DOI
Rui Jiang, Jiayi Guo, Shenglan Yang

и другие.

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

Trichoderma reesei, recognized by the FDA as a food-safe strain, plays vital role in food fermentation. Although enzymatic applications of T. reesei are well-established, health benefits its fermentation-derived metabolites yet to be fully explored. Trichodenoids A (1) and B (2), two skeletally unprecedented polyketides, were isolated from endophytic fungus originating plant Gastrodia elata Blume. Their structures elucidated via spectroscopic data, single-crystal X-ray crystallographic analysis, quantum chemical DP4+ ECD calculation. Compounds 1 2 uniquely defined unusual 6/6/5 6/6/5/6 ring systems, respectively, which proposed formed through key Diels-Alder Baeyer-Villiger reactions during biosynthesis. Compound had potential mitigate H2O2-induced oxidative stress H9C2 cells reducing intracellular ROS levels, restoring mitochondrial function, regulating mRNA expression related stress, inflammation, autophagy. These findings highlight compound candidate for natural antioxidants even dietary supplements cardiovascular health.

Язык: Английский

Процитировано

0

Comparative Genomic Analysis Reveals Key Changes in the Genome of Acremonium chrysogenum That Occurred During Classical Strain Improvement for Production of Antibiotic Cephalosporin C DOI Open Access
Alexander A. Zhgun

International Journal of Molecular Sciences, Год журнала: 2024, Номер 26(1), С. 181 - 181

Опубликована: Дек. 28, 2024

From the 1950s to present, main tool for obtaining fungal industrial producers of secondary metabolites remains so-called classical strain improvement (CSI) methods associated with multi-round random mutagenesis and screening level target products. As a result application such techniques, yield in high-yielding (HY) strains was increased hundreds times compared wild-type (WT) parental strains. However, events that occur at molecular during CSI programs are still unknown. In this paper, an attempt made identify characteristic changes genome occurred

Язык: Английский

Процитировано

0