한빛사 논문
Donghyuk Kim1,2,*,†, Sang Woo Seo1,3,†, Ye Gao4,†, Hojung Nam5, Gabriela I. Guzman1, Byung-Kwan Cho6,8 and Bernhard O. Palsson1,7,8,*
1Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA, 2Department of Genetic Engineering, College of Life Sciences, Kyung Hee University, Yongin 446–701, Republic of Korea, 3School of Chemical and Biological Engineering, Institute of Chemical Prcocess, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea, 4Division of Biological Science, University of California, San Diego, La Jolla, CA 92093, USA, 5School of Information and Communication, Gwangju Institute of Science and Technology, 123 Cheomdan-gwagiro, Buk-gu, Gwangju, Republic of Korea, 6Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea, 7Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA and 8The Novo Nordisk Foundation Center for Biosustainabiliy, Danish Technical University, 6 Kogle Alle, Hørsholm, Denmark
*To whom correspondence should be addressed.
Correspondence may also be addressed to Donghyuk Kim.
†These authors contributed equally to this work as first authors.
Abstract
Two major transcriptional regulators of carbon metabolism in bacteria are Cra and CRP. CRP is considered to be the main mediator of catabolite repression. Unlike for CRP, in vivo DNA binding information of Cra is scarce. Here we generate and integrate ChIP-exo and RNA-seq data to identify 39 binding sites for Cra and 97 regulon genes that are regulated by Cra in Escherichia coli. An integrated metabolic-regulatory network was formed by including experimentally-derived regulatory information and a genome-scale metabolic network reconstruction. Applying analysis methods of systems biology to this integrated network showed that Cra enables optimal bacterial growth on poor carbon sources by redirecting and repressing glycolysis flux, by activating the glyoxylate shunt pathway, and by activating the respiratory pathway. In these regulatory mechanisms, the overriding regulatory activity of Cra over CRP is fundamental. Thus, elucidation of interacting transcriptional regulation of core carbon metabolism in bacteria by two key transcription factors was possible by combining genome-wide experimental measurement and simulation with a genome-scale metabolic model.
논문정보
관련 링크
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기