A dynamic flux balance model and bottleneck identification of glucose, xylose, xylulose co-fermentation in Saccharomyces cerevisiae

Hohenschuh, William; Hector, Ronald E.; Murthy, Ganti S.

doi:10.1016/j.biortech.2015.02.015

Cited by 20 publications

(10 citation statements)

References 19 publications

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“…We believe that models based on FBA also have great potential to be expanded from QSSA in order to describe the dynamics of metabolic pathways. So-called dynamic FBA allows one to track the time dependent behavior of fluxes and has been performed for several systems including E. coli (Barreto-Rodriguez et al, 2014, Grafahrend-Belau et al, 2013, Hohenschuh et al, 2015, Mahadevan et al, 2002. By looking at fluxes over time, the models become much more similar to the more quantitative kinetic models (Table 1), without the need for kinetic parameters.…”

Section: Relevance Of Computational Models To Lipid Biosynthesismentioning

confidence: 99%

Current advances in molecular, biochemical, and computational modeling analysis of microalgal triacylglycerol biosynthesis

Lenka

Carbonaro

Park

et al. 2016

Biotechnology Advances

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Triacylglycerols (TAGs) are highly reduced energy storage molecules ideal for biodiesel production. Microalgal TAG biosynthesis has been studied extensively in recent years, both at the molecular level and systems level through experimental studies and computational modeling. However, discussions of the strategies and products of the experimental and modeling approaches are rarely integrated and summarized together in a way that promotes collaboration among modelers and biologists in this field. In this review, we outline advances toward understanding the cellular and molecular factors regulating TAG biosynthesis in unicellular microalgae with an emphasis on recent studies on rate-limiting steps in fatty acid and TAG synthesis, while also highlighting new insights obtained from the integration of multi-omics datasets with mathematical models. Computational methodologies such as kinetic modeling, metabolic flux analysis, and new variants of flux balance analysis are explained in detail. We discuss how these methods have been used to simulate algae growth and lipid metabolism in response to changing culture conditions and how they have been used in conjunction with experimental validations. Since emerging evidence indicates that TAG synthesis in microalgae operates through coordinated crosstalk between multiple pathways in diverse subcellular destinations including the endoplasmic reticulum and plastids, we discuss new experimental studies and models that incorporate these findings for discovering key regulatory checkpoints. Finally, we describe tools for genetic manipulation of microalgae and their potential for future rational algal strain design. This comprehensive review explores the potential synergistic impact of pathway analysis, computational approaches, and molecular genetic manipulation strategies on improving TAG production in microalgae.

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Section: Relevance Of Computational Models To Lipid Biosynthesismentioning

confidence: 99%

Current advances in molecular, biochemical, and computational modeling analysis of microalgal triacylglycerol biosynthesis

Lenka

Carbonaro

Park

et al. 2016

Biotechnology Advances

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“…Unfortunately, these interesting results of clear biotechnological implications have not been further explored (Mittelman & Barkai, ). Another issue that has not been explored is how xylulose enters the yeasts cell, and although it is assumed that xylulose is probably transported by sugar (hexose) transporters, a hxt ‐null strain deleted in the major hexose transporters present in S. cerevisiae ( HXT1 to HXT7 ) is still able to consume xylulose with rates that correspond to >50% of those observed in wild‐type strains (Hohenschuh, Hector, & Murthy, ), suggesting that xylulose uptake is probably mediated by other permeases present in yeast cells. Indeed, in solution the open chain form of xylulose cyclizes to form α‐ or β‐ d ‐xylulofuranose (Figure ), which is different from the pyranose rings formed by hexoses (or xylose) in solution, the structure recognized and transported by canonical HXT permeases.…”

Section: Pentose Fermentation By S Cerevisiaementioning

confidence: 99%

d‐Xylose consumption by nonrecombinant Saccharomyces cerevisiae: A review

Patiño

Ortiz

Velásquez

et al. 2019

Yeast

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Xylose is the second most abundant sugar in nature. Its efficient fermentation has been considered as a critical factor for a feasible conversion of renewable biomass resources into biofuels and other chemicals. The yeast Saccharomyces cerevisiae is of exceptional industrial importance due to its excellent capability to ferment sugars. However, although S. cerevisiae is able to ferment xylulose, it is considered unable to metabolize xylose, and thus, a lot of research has been directed to engineer this yeast with heterologous genes to allow xylose consumption and fermentation. The analysis of the natural genetic diversity of this yeast has also revealed some nonrecombinant S. cerevisiae strains that consume or even grow (modestly) on xylose. The genome of this yeast has all the genes required for xylose transport and metabolism through the xylose reductase, xylitol dehydrogenase, and xylulokinase pathway, but there seems to be problems in their kinetic properties and/or required expression. Self‐cloning industrial S. cerevisiae strains overexpressing some of the endogenous genes have shown interesting results, and new strategies and approaches designed to improve these S. cerevisiae strains for ethanol production from xylose will also be presented in this review.

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“…29 Briefly, the xylulose is transported by the hexose transporter family into the cells, which is then phosphorylated and through the pentose phosphate pathway (PPP) moves in to the central metabolism system. 30 Similar to glucose, xylulose may also be utilized for respiration or fermentation. This was exemplified by Mittelman and Barkai, 31 in which yeast cells (S. cerevisiae) that were grown on xylulose participated in activation of the transcription characteristic of respiring cells rather than fermenting cells.…”

Section: Carbon Sourcesmentioning

confidence: 99%

Influence of reactors, microbial carbohydrate uptake, and metabolic pathways on ethanol production from grass biomass: A review

et al. 2018

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Summary Grasses are considered to be potential lignocellulosic feedstock for renewable and sustainable biofuels such as bioethanol. However, the process involved, ie, pretreatment, enzymatic saccharification, and fermentation in conversion of these lignocellulosic biomass to bioethanol, remains expensive and at present is not affordable for industrial production. Thus, the present review assesses the influence of the recent technologies that can be employed for the bio‐refinery based pretreatment and enzymatic hydrolysis of grass biomass using advanced bioreactors. Since plant extracts have been seen to enhance the glucose uptake, an experiment was implemented to elucidate the role of plant extracts (bark extracts of Xylocarpus granatum) on glucose uptake capacity of microorganisms like Saccharomyces cerevisiae, Pichia sp., and Zymomonas mobilis and their subsequent ethanol production capability from glucose and xylose sugars. The results of these experiments indicated that supplementation of plant extracts promoted both glucose and xylose uptake in S. cerevisiae and Pichia sp. as compared with the control and Z. mobilis strain. Further, as Pichia sp. exhibited good uptake ability for both glucose and xylose, a model was proposed focusing on the gene silencing and operon concept in Pichia sp. for preferential pentose utilization during the fermentation of grass biomass to bioethanol.

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A dynamic flux balance model and bottleneck identification of glucose, xylose, xylulose co-fermentation in Saccharomyces cerevisiae

Cited by 20 publications

References 19 publications

Current advances in molecular, biochemical, and computational modeling analysis of microalgal triacylglycerol biosynthesis

Current advances in molecular, biochemical, and computational modeling analysis of microalgal triacylglycerol biosynthesis

d‐Xylose consumption by nonrecombinant Saccharomyces cerevisiae: A review

Influence of reactors, microbial carbohydrate uptake, and metabolic pathways on ethanol production from grass biomass: A review

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