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An efficient system for intestinal on-site butyrate production using novel microbiome-derived esterases

Authors
 Dah Hyun Jung  ;  Ji Hyun Yong  ;  Wontae Hwang  ;  Mi Young Yoon  ;  Sang Sun Yoon 
Citation
 JOURNAL OF BIOLOGICAL ENGINEERING, Vol.15(1) : 9, 2021-03 
Journal Title
JOURNAL OF BIOLOGICAL ENGINEERING
Issue Date
2021-03
Keywords
Bacteroidales ; Butyrate ; Clostridiales ; Colitis ; Esterase ; Inflammatory bowel disease (IBD) ; Metagenomic library ; Microbiome ; Prodrug ; Tributyrin
Abstract
Short-chain fatty acids, especially butyrate, play beneficial roles in sustaining gastrointestinal health. However, due to limitations associated with direct consumption of butyrate, there has been interest in using prodrugs of butyrate. Tributyrin (TB), a triglyceride composed of three butyrate molecules and a glycerol, is a well-studied precursor of butyrate. We screened a metagenome library consisting of 5760 bacterial artificial chromosome clones, with DNA inserts originating from mouse microbiomes, and identified two clones that efficiently hydrolyse TB into butyrate. Nucleotide sequence analysis indicated that inserts in these two clones are derived from unknown microbes. BLASTp analysis, however, revealed that each insert contains a gene homologous to acetylesterase or esterase genes, from Clostridium spp. and Bacteroides spp., respectively. Predicted structures of these two proteins both contain serine-histidine-aspartate catalytic triad, highly conserved in the family of esterases. Escherichia coli host expressing each of the two candidate genes invariably produced greater amounts of butyrate in the presence of TB. Importantly, administration of TB together with cloned E. coli cells alleviated inflammatory symptoms in a mouse model of acute colitis. Based on these results, we established an efficient on-site and real-time butyrate production system that releases butyrate in a controlled manner inside the intestine.
Files in This Item:
T202102489.pdf Download
DOI
10.1186/s13036-021-00259-4
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Mi Young(윤미영)
Yoon, Sang Sun(윤상선) ORCID logo https://orcid.org/0000-0003-2979-365X
Hwang, Wontae(황원태)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184186
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