Engineering Bacteroides thetaiotaomicron to produce non-native butyrate based on a genome-scale metabolic model-guided design = 게놈 규모의 대사모델 설계 기반의 부티레이트 생산 박테로이데스 균주 엔지니어링

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dc.contributor.authorK Kim-
dc.contributor.authorD Choe-
dc.contributor.authorY Song-
dc.contributor.authorM Kang-
dc.contributor.authorSeung Goo Lee-
dc.contributor.authorDae Hee Lee-
dc.contributor.authorB K Cho-
dc.date.accessioned2021-10-19T15:31:02Z-
dc.date.available2021-10-19T15:31:02Z-
dc.date.issued2021-
dc.identifier.issn10967176-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/24926-
dc.description.abstractBacteroides thetaiotaomicron represents a major symbiont of the human gut microbiome that is increasingly viewed as a promising candidate strain for microbial therapeutics. Here, we engineer B. thetaiotaomicron for heterologous production of non-native butyrate as a proof-of-concept biochemical at therapeutically relevant concentrations. Since B. thetaiotaomicron is not a natural producer of butyrate, we heterologously expressed a butyrate biosynthetic pathway in the strain, which led to the production of butyrate at the final concentration of 12 mg/L in a rich medium. Further optimization of butyrate production was achieved by a round of metabolic engineering guided by an expanded genome-scale metabolic model (GEM) of B. thetaiotaomicron. The in silico knock-out simulation of the expanded model showed that pta and ldhD were the potent knock-out targets to enhance butyrate production. The maximum titer and specific productivity of butyrate in the pta-ldhD double knockout mutant increased by nearly 3.4 and 4.8 folds, respectively. To our knowledge, this is the first engineering attempt that enabled butyrate production from a non-butyrate producing commensal B. thetaiotaomicron. The study also highlights that B. thetaiotaomicron can serve as an effective strain for live microbial therapeutics in human.-
dc.publisherElsevier-
dc.titleEngineering Bacteroides thetaiotaomicron to produce non-native butyrate based on a genome-scale metabolic model-guided design = 게놈 규모의 대사모델 설계 기반의 부티레이트 생산 박테로이데스 균주 엔지니어링-
dc.title.alternativeEngineering Bacteroides thetaiotaomicron to produce non-native butyrate based on a genome-scale metabolic model-guided design-
dc.typeArticle-
dc.citation.titleMetabolic Engineering-
dc.citation.number0-
dc.citation.endPage186-
dc.citation.startPage174-
dc.citation.volume68-
dc.contributor.affiliatedAuthorSeung Goo Lee-
dc.contributor.affiliatedAuthorDae Hee Lee-
dc.contributor.alternativeName김강산-
dc.contributor.alternativeName채동희-
dc.contributor.alternativeName송요셉-
dc.contributor.alternativeName강민정-
dc.contributor.alternativeName이승구-
dc.contributor.alternativeName이대희-
dc.contributor.alternativeName조병관-
dc.identifier.bibliographicCitationMetabolic Engineering, vol. 68, pp. 174-186-
dc.identifier.doi10.1016/j.ymben.2021.10.005-
dc.subject.keywordBacteroides thetaiotaomicron-
dc.subject.keywordGenome-scale metabolic model-
dc.subject.keywordFlux-balance analysis-
dc.subject.keywordButyrate-
dc.subject.keywordCommensal microbes-
dc.subject.localBacteroides thetaiotaomicron-
dc.subject.localButyrate-
dc.description.journalClassY-
Appears in Collections:
Division of Biomaterials Research > 1. Journal Articles
Division of Biomaterials Research > Synthetic Biology and Bioengineering Research Center > 1. Journal Articles
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