Leveraging core enzyme structures for microbiota targeted functional regulation: Urease as an example DOI Creative Commons
Shengguo Zhao,

Huiyue Zhong,

Yue He

et al.

iMeta, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract Microbial communities play critical roles in various ecosystems. Despite extensive research on the taxonomic and functional diversity of microbial communities, effective approaches to regulate targeted functions remain limited. Here, we present an innovative methodology that integrates core enzyme identification, protein structural characterization, regulator virtual screening, validation achieve precise microbiome regulation. As a proof concept, focused regulation urea decomposition by rumen microbiota ruminants. Through metagenomic analysis, identified urease gene its corresponding genome (MAG257) affiliated with unclassified Succinivibrionaceae, reconstructed complete cluster. Structural analysis catalytic subunit (UreC) via cryo‐electron microscopy (cryo‐EM) revealed detailed features active site, guiding molecular docking studies epiberberine, natural compound potent inhibitory activity. Validation simulation system demonstrated epiberberine significantly reduced enhanced nitrogen utilization. This study establishes robust framework combines biology computational screening regulation, offering promising tool for engineering broader applications animal productivity, human health, environmental improvement, biotechnology.

Language: Английский

Reductive acetogenesis is a dominant process in the ruminant hindgut DOI Creative Commons
Qiushuang Li,

Jiabin Huo,

Gaofeng Ni

et al.

Microbiome, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 28, 2025

The microbes residing in ruminant gastrointestinal tracts play a crucial role converting plant biomass to volatile fatty acids, which serve as the primary energy source for ruminants. This tract comprises foregut (rumen) and hindgut (cecum colon), differ structures functions, particularly with respect feed digestion fermentation. While rumen microbiome has been extensively studied, cecal remains much less investigated understood, especially concerning assembling microbial communities overriding pathways of hydrogen metabolism. To address this gap, we comparatively composition, capabilities, activities cecum using goats an experimental model. In situ measurements showed significantly higher levels dissolved acetate than rumen. Increased indicated distinct processes reduced coupling between fermentative H2 production utilization, whereas could be caused by slower VFA absorption through papillae papillae. Microbial profiling that harbors greater abundance mucin-degrading producers, contains fibrolytic bacteria, hydrogenotrophic respiratory methanogenic archaea. Most strikingly, reductive acetogenic bacteria were 12-fold more abundant cecum. Genome-resolved metagenomic analysis unveiled acetogens are both phylogenetically functionally from those found Further supporting these findings, two vitro experiments demonstrated marked difference metabolism rumen, increased methanogenesis Moreover, comparative across multiple species confirmed strong enrichment hindguts, suggesting conserved functional role. These findings highlight acetogenesis key region reshape our understanding how can managed accord livestock methane mitigation efforts.

Language: Английский

Citations

0

Maternal undernutrition inhibits fetal rumen development: Novel miRNA-736-mediated dual targeting of E2F2 and MYBL2 in sheep DOI
Peng Jiao, Yun Xu,

Yun‐Qiong Gu

et al.

Published: May 13, 2025

Abstract Background Undernutrition disrupts pregnant ewe’s metabolic homeostasis and severely inhibits fetal growth development. In this study, undernourished nutrition-recovery sheep models rumen epithelial cells were utilized to investigate the mechanisms behind undernutrition-induced disruptions in metabolism Results Maternal undernutrition significantly reduced weight papilla length, width surface area. extremely suppressed nutrient energy production via JAK3/STAT3 signaling inhibit cell cycle progression development, while maternal nutritional recovery partially restored inhibition but failed alleviate Meanwhile, 64 differentially expressed miRNAs (DEMs) identified between ewes controls. Novel miR-736 was overexpressed both of models. E2F transcription factor 2 (E2F2) MYB proto-oncogene like (MYBL2) intersection genes (DEGs) DEMs target integrated analysis predicted as genes. Further, we confirmed that targeted downregulated E2F2 MYBL2 expressional levels. Silencing promoted apoptosis inhibited S-phase entry cells. Conclusions summary, disrupted elevated miR-736, which promote apoptosis, finally This study provides new insights into epigenetic underlying developmental deficits.

Language: Английский

Citations

0

Leveraging core enzyme structures for microbiota targeted functional regulation: Urease as an example DOI Creative Commons
Shengguo Zhao,

Huiyue Zhong,

Yue He

et al.

iMeta, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract Microbial communities play critical roles in various ecosystems. Despite extensive research on the taxonomic and functional diversity of microbial communities, effective approaches to regulate targeted functions remain limited. Here, we present an innovative methodology that integrates core enzyme identification, protein structural characterization, regulator virtual screening, validation achieve precise microbiome regulation. As a proof concept, focused regulation urea decomposition by rumen microbiota ruminants. Through metagenomic analysis, identified urease gene its corresponding genome (MAG257) affiliated with unclassified Succinivibrionaceae, reconstructed complete cluster. Structural analysis catalytic subunit (UreC) via cryo‐electron microscopy (cryo‐EM) revealed detailed features active site, guiding molecular docking studies epiberberine, natural compound potent inhibitory activity. Validation simulation system demonstrated epiberberine significantly reduced enhanced nitrogen utilization. This study establishes robust framework combines biology computational screening regulation, offering promising tool for engineering broader applications animal productivity, human health, environmental improvement, biotechnology.

Language: Английский

Citations

0