Serial adaptive laboratory evolution enhances mixed carbon metabolic capacity of Escherichia coli.

Autor: Kim K; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea; KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea., Choe D; Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA., Kang M; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea; KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea., Cho SH; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea; KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea., Cho S; KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea., Jeong KJ; KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea; Graduate School of Engineering Biology, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea., Palsson B; Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA; Department of Pediatrics, University of California San Diego, La Jolla, CA, 92093, USA., Cho BK; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea; KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea; Graduate School of Engineering Biology, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea. Electronic address: bcho@kaist.ac.kr.
Jazyk: angličtina
Zdroj: Metabolic engineering [Metab Eng] 2024 May; Vol. 83, pp. 160-171. Date of Electronic Publication: 2024 Apr 16.
DOI: 10.1016/j.ymben.2024.04.004
Abstrakt: Microbes have inherent capacities for utilizing various carbon sources, however they often exhibit sub-par fitness due to low metabolic efficiency. To test whether a bacterial strain can optimally utilize multiple carbon sources, Escherichia coli was serially evolved in L-lactate and glycerol. This yielded two end-point strains that evolved first in L-lactate then in glycerol, and vice versa. The end-point strains displayed a universal growth advantage on single and a mixture of adaptive carbon sources, enabled by a concerted action of carbon source-specialists and generalist mutants. The combination of just four variants of glpK, ppsA, ydcI, and rph-pyrE, accounted for more than 80% of end-point strain fitness. In addition, machine learning analysis revealed a coordinated activity of transcriptional regulators imparting condition-specific regulation of gene expression. The effectiveness of the serial adaptive laboratory evolution (ALE) scheme in bioproduction applications was assessed under single and mixed-carbon culture conditions, in which serial ALE strain exhibited superior productivity of acetoin compared to ancestral strains. Together, systems-level analysis elucidated the molecular basis of serial evolution, which hold potential utility in bioproduction applications.
Competing Interests: Declaration of competing interest There are no conflicts to declare.
(Copyright © 2024 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE