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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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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. |
format | Online Article Text |
id | pubmed-5805702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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