Redirection of the Glycolytic Flux Enhances Isoprenoid Production in Saccharomyces cerevisiae
Abstract
Abstract Sufficient supply of reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a prerequisite of the overproduction of isoprenoids and related bioproducts in Saccharomyces cerevisiae . Although S. cerevisiae highly depends on the oxidative pentose phosphate (PP) pathway to produce NADPH, its metabolic flux toward the oxidative PP pathway is limited due to the rigid glycolysis flux. To maximize NADPH supply for the isoprenoid production in yeast, upper glycolytic metabolic fluxes are reduced by introducing mutations into phosphofructokinase (PFK) along with overexpression of ZWF1 encoding glucose‐6‐phosphate (G6P) dehydrogenase. The PFK mutations (Pfk1 S724D and Pfk2 S718D) result in less glycerol production and more accumulation of G6P, which is a gateway metabolite toward the oxidative PP pathway. When combined with the PFK mutations, overexpression of ZWF1 caused substantial increases of [NADPH]/[NADP + ] ratios whereas the effect of ZWF1 overexpression alone in the wild‐type strain is not noticeable. Also, the introduction of ZWF1 overexpression and the PFK mutations into engineered yeast overexpressing acetyl‐CoA C‐acetyltransferase ( ERG10 ), truncated HMG‐CoA reductase isozyme 1 ( tHMG1 ), and amorphadiene synthase ( ADS ) leads to a titer of 497 mg L –1 of amorphadiene (3.7‐fold over the parental strain). These results suggest that perturbation ofmore »
- Authors:
-
[1];
[1]
- Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Food Science and Human Nutrition and Carl R. Woese Institute for Genomic Biology
- Univ. of Illinois, Urbana-Champaign, IL (United States). Carl R. Woese Institute for Genomic Biology; Korea Univ., Seoul (Korea). Dept. of Biotechnology
- Korea Univ., Seoul (Korea). Dept. of Biotechnology
- Publication Date:
- Research Org.:
- Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1559936
- Alternate Identifier(s):
- OSTI ID: 1562316
- Grant/Contract Number:
- SC0018420; DE‐SC0018420
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Biotechnology Journal
- Additional Journal Information:
- Journal Volume: none; Journal Issue: none; Journal ID: ISSN 1860-6768
- Publisher:
- Wiley
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; isoprenoid, NADPH, oxidative pentose phosphate pathway, phosphofructokinase, Saccharomyces cerevisiae
Citation Formats
Kwak, Suryang, Yun, Eun Ju, Lane, Stephan, Oh, Eun Joong, Kim, Kyoung Heon, and Jin, Yong‐Su. Redirection of the Glycolytic Flux Enhances Isoprenoid Production in Saccharomyces cerevisiae. United States: N. p., 2019.
Web. doi:10.1002/biot.201900173.
Kwak, Suryang, Yun, Eun Ju, Lane, Stephan, Oh, Eun Joong, Kim, Kyoung Heon, & Jin, Yong‐Su. Redirection of the Glycolytic Flux Enhances Isoprenoid Production in Saccharomyces cerevisiae. United States. https://doi.org/10.1002/biot.201900173
Kwak, Suryang, Yun, Eun Ju, Lane, Stephan, Oh, Eun Joong, Kim, Kyoung Heon, and Jin, Yong‐Su. Thu .
"Redirection of the Glycolytic Flux Enhances Isoprenoid Production in Saccharomyces cerevisiae". United States. https://doi.org/10.1002/biot.201900173. https://www.osti.gov/servlets/purl/1559936.
@article{osti_1559936,
title = {Redirection of the Glycolytic Flux Enhances Isoprenoid Production in Saccharomyces cerevisiae},
author = {Kwak, Suryang and Yun, Eun Ju and Lane, Stephan and Oh, Eun Joong and Kim, Kyoung Heon and Jin, Yong‐Su},
abstractNote = {Abstract Sufficient supply of reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a prerequisite of the overproduction of isoprenoids and related bioproducts in Saccharomyces cerevisiae . Although S. cerevisiae highly depends on the oxidative pentose phosphate (PP) pathway to produce NADPH, its metabolic flux toward the oxidative PP pathway is limited due to the rigid glycolysis flux. To maximize NADPH supply for the isoprenoid production in yeast, upper glycolytic metabolic fluxes are reduced by introducing mutations into phosphofructokinase (PFK) along with overexpression of ZWF1 encoding glucose‐6‐phosphate (G6P) dehydrogenase. The PFK mutations (Pfk1 S724D and Pfk2 S718D) result in less glycerol production and more accumulation of G6P, which is a gateway metabolite toward the oxidative PP pathway. When combined with the PFK mutations, overexpression of ZWF1 caused substantial increases of [NADPH]/[NADP + ] ratios whereas the effect of ZWF1 overexpression alone in the wild‐type strain is not noticeable. Also, the introduction of ZWF1 overexpression and the PFK mutations into engineered yeast overexpressing acetyl‐CoA C‐acetyltransferase ( ERG10 ), truncated HMG‐CoA reductase isozyme 1 ( tHMG1 ), and amorphadiene synthase ( ADS ) leads to a titer of 497 mg L –1 of amorphadiene (3.7‐fold over the parental strain). These results suggest that perturbation of upper glycolytic fluxes, in addition to ZWF1 overexpression, is necessary for efficient NADPH supply through the oxidative PP pathway and enhanced production of isoprenoids by engineered S. cerevisiae .},
doi = {10.1002/biot.201900173},
journal = {Biotechnology Journal},
number = none,
volume = none,
place = {United States},
year = {2019},
month = {8}
}
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