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Glucose repression can be alleviated by reducing glucose phosphorylation rate in Saccharomyces cerevisiae

Microorganisms commonly exhibit preferential glucose consumption and diauxic growth when cultured in mixtures of glucose and other sugars. Although various genetic perturbations have alleviated the effects of glucose repression on consumption of specific sugars, a broadly applicable mechanism remain...

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Autores principales: Lane, Stephan, Xu, Haiqing, Oh, Eun Joong, Kim, Heejin, Lesmana, Anastashia, Jeong, Deokyeol, Zhang, Guochang, Tsai, Ching-Sung, Jin, Yong-Su, Kim, Soo Rin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805702/
https://www.ncbi.nlm.nih.gov/pubmed/29422502
http://dx.doi.org/10.1038/s41598-018-20804-4
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author Lane, Stephan
Xu, Haiqing
Oh, Eun Joong
Kim, Heejin
Lesmana, Anastashia
Jeong, Deokyeol
Zhang, Guochang
Tsai, Ching-Sung
Jin, Yong-Su
Kim, Soo Rin
author_facet Lane, Stephan
Xu, Haiqing
Oh, Eun Joong
Kim, Heejin
Lesmana, Anastashia
Jeong, Deokyeol
Zhang, Guochang
Tsai, Ching-Sung
Jin, Yong-Su
Kim, Soo Rin
author_sort Lane, Stephan
collection PubMed
description Microorganisms commonly exhibit preferential glucose consumption and diauxic growth when cultured in mixtures of glucose and other sugars. Although various genetic perturbations have alleviated the effects of glucose repression on consumption of specific sugars, a broadly applicable mechanism remains unknown. Here, we report that a reduction in the rate of glucose phosphorylation alleviates the effects of glucose repression in Saccharomyces cerevisiae. Through adaptive evolution under a mixture of xylose and the glucose analog 2-deoxyglucose, we isolated a mutant strain capable of simultaneously consuming glucose and xylose. Genome sequencing of the evolved mutant followed by CRISPR/Cas9-based reverse engineering revealed that mutations in the glucose phosphorylating enzymes (Hxk1, Hxk2, Glk1) were sufficient to confer simultaneous glucose and xylose utilization. We then found that varying hexokinase expression with an inducible promoter led to the simultaneous utilization of glucose and xylose. Interestingly, no mutations in sugar transporters occurred during the evolution, and no specific transporter played an indispensable role in simultaneous sugar utilization. Additionally, we demonstrated that slowing glucose consumption also enabled simultaneous utilization of glucose and galactose. These results suggest that the rate of intracellular glucose phosphorylation is a decisive factor for metabolic regulations of mixed sugars.
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spelling pubmed-58057022018-02-16 Glucose repression can be alleviated by reducing glucose phosphorylation rate in Saccharomyces cerevisiae Lane, Stephan Xu, Haiqing Oh, Eun Joong Kim, Heejin Lesmana, Anastashia Jeong, Deokyeol Zhang, Guochang Tsai, Ching-Sung Jin, Yong-Su Kim, Soo Rin Sci Rep Article Microorganisms commonly exhibit preferential glucose consumption and diauxic growth when cultured in mixtures of glucose and other sugars. Although various genetic perturbations have alleviated the effects of glucose repression on consumption of specific sugars, a broadly applicable mechanism remains unknown. Here, we report that a reduction in the rate of glucose phosphorylation alleviates the effects of glucose repression in Saccharomyces cerevisiae. Through adaptive evolution under a mixture of xylose and the glucose analog 2-deoxyglucose, we isolated a mutant strain capable of simultaneously consuming glucose and xylose. Genome sequencing of the evolved mutant followed by CRISPR/Cas9-based reverse engineering revealed that mutations in the glucose phosphorylating enzymes (Hxk1, Hxk2, Glk1) were sufficient to confer simultaneous glucose and xylose utilization. We then found that varying hexokinase expression with an inducible promoter led to the simultaneous utilization of glucose and xylose. Interestingly, no mutations in sugar transporters occurred during the evolution, and no specific transporter played an indispensable role in simultaneous sugar utilization. Additionally, we demonstrated that slowing glucose consumption also enabled simultaneous utilization of glucose and galactose. These results suggest that the rate of intracellular glucose phosphorylation is a decisive factor for metabolic regulations of mixed sugars. Nature Publishing Group UK 2018-02-08 /pmc/articles/PMC5805702/ /pubmed/29422502 http://dx.doi.org/10.1038/s41598-018-20804-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lane, Stephan
Xu, Haiqing
Oh, Eun Joong
Kim, Heejin
Lesmana, Anastashia
Jeong, Deokyeol
Zhang, Guochang
Tsai, Ching-Sung
Jin, Yong-Su
Kim, Soo Rin
Glucose repression can be alleviated by reducing glucose phosphorylation rate in Saccharomyces cerevisiae
title Glucose repression can be alleviated by reducing glucose phosphorylation rate in Saccharomyces cerevisiae
title_full Glucose repression can be alleviated by reducing glucose phosphorylation rate in Saccharomyces cerevisiae
title_fullStr Glucose repression can be alleviated by reducing glucose phosphorylation rate in Saccharomyces cerevisiae
title_full_unstemmed Glucose repression can be alleviated by reducing glucose phosphorylation rate in Saccharomyces cerevisiae
title_short Glucose repression can be alleviated by reducing glucose phosphorylation rate in Saccharomyces cerevisiae
title_sort glucose repression can be alleviated by reducing glucose phosphorylation rate in saccharomyces cerevisiae
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805702/
https://www.ncbi.nlm.nih.gov/pubmed/29422502
http://dx.doi.org/10.1038/s41598-018-20804-4
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