Saccharomyces cerevisiae: a potential host for carboxylic acid production from lignocellulosic feedstock?

Sandström, Anders; Almqvist, Henrik; Portugal-Nunes, Diogo; Neves, Dário; Lidén, Gunnar; Gorwa-Grauslund, Marie-Françoise

doi:10.1007/s00253-014-5866-5

Cited by 20 publications

(13 citation statements)

References 142 publications

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“…109 Annual production of these compounds is as follows (ktons): acetic acid: 10 000; acrylic acid: 4200; 3-hydroxypropionic acid: 3600; adipic acid: 3000; citric acid: 1600; lactic acid: 450; fumaric acid: 200; gluconic acid: 87; itaconic acid: 80; malic acid: 60; glucaric acid: 42; glycolic acid: 40; and succinic acid: 37. Acetic and lactic acids are used as food preservatives.…”

Section: Organic Acidsmentioning

confidence: 99%

Production of valuable compounds by molds and yeasts

Demain

Martens

2016

J Antibiot

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where he has contributed in a major way to the reputation of this department for many years. He also served as an Adjunct Professor at the University of Geneva. Among Julian's areas of study and accomplishment are fungal toxins including α-sarcin, chemical synthesis of triterpenes, mode of action of streptomycin and other aminoglycoside antibiotics, biochemical mechanisms of antibiotic resistance in clinical isolates of bacteria harboring resistance plasmids, their origins and evolution, secondary metabolism of microorganisms, structure and function of bacterial ribosomes, antibiotic resistance mutations in yeast ribosomes, cloning of resistance genes from an antibiotic-producing microbe, gene cloning for industrial purposes, engineering of herbicide resistance in useful crops, bleomycin-resistance gene in clinical isolates of Staphylococcus aureus and many other topics. He has been an excellent teacher, lecturing in both English and French around the world, and has organized international courses. Julian has also served on the NIH study sections, as Editor for several international journals, and was one of the founders of the journal Plasmid. We expect the impact of Julian's accomplishments to continue into the future.

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Section: Organic Acidsmentioning

confidence: 99%

Production of valuable compounds by molds and yeasts

Demain

Martens

2016

J Antibiot

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“…Baker’s yeast, Saccharomyces cerevisiae, can be used for production of a range of different commodity chemicals [1], [44], biofuels [20], [25], [41], bioflavours [8], fine chemicals [45], [46], [54] and pharmaceuticals [17], [53]. It is used as production host for approximately 20% of biopharmaceuticals approved by the Food and Drug Administration (FDA) or by the European Medicines Agency (EMA) [15].…”

Section: Introductionmentioning

confidence: 99%

Exploring the potential of the glycerol-3-phosphate dehydrogenase 2 (GPD2) promoter for recombinant gene expression in Saccharomyces cerevisiae

Knudsen

Johanson

Lantz

et al. 2015

Biotechnology Reports

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A control point for keeping redox homeostasis in Saccharomyces cerevisiae during fermentative growth is the dynamic regulation of transcription for the glycerol-3-phosphate dehydrogenase 2 (GPD2) gene. In this study, the possibility to steer the activity of the GPD2 promoter was investigated by placing it in strains with different ability to reoxidise NADH, and applying different environmental conditions. Flow cytometric analysis of reporter strains expressing green fluorescent protein (GFP) under the control of the GPD2 promoter was used to determine the promoter activity at the single-cell level. When placed in a gpd1Δgpd2Δ strain background, the GPD2 promoter displayed a 2-fold higher activity as compared to the strong constitutive glyceraldehyde-3-phosphate dehydrogenase (TDH3). In contrast, the GPD2 promoter was found to be inactive when cells were cultivated in continuous mode at a growth rate of 0.3 h−1 and in conditions with excess oxygen (i.e. with an aeration of 2.5 vvm, and a stirring of 800 rpm). In addition, a clear window of operation where the gpd1Δgpd2Δ strain can be grown with the same efficiency as wild type yeast was identified. In conclusion, the flow cytometry mapping revealed conditions where the GPD2 promoter was either completely inactive or hyperactive, which has implications for its implementation in future biotechnological applications such as for process control of heterologous gene expression.

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“…This indicates the importance of a more efficient product exporter. This prominence of examining transport processes, such as substrate uptake and product export, possibly coupled to cellular energetics, for microbial organic acid production was mentioned for various organic acids in different host organisms (Beauprez et al, ; Sandström et al, ; Sauer et al, ). Therefore, an even more powerful succinate exporter and the elimination of residual succinate import activity should be the first new targets, because it has been shown that central metabolism is flexible enough to accommodate large changes in fluxes.…”

Section: Resultsmentioning

confidence: 99%

Comparative fluxome and metabolome analysis for overproduction of succinate in Escherichia coli

Taymaz-Nikerel

Mey

Baart

et al. 2015

Biotech & Bioengineering

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An aerobic succinate-producing Escherichia coli mutant was compared to its wild-type by quantitatively analyzing both the metabolome and fluxome, during glucose-limited steady-state and succinate excess dynamic conditions, in order to identify targets for further strain engineering towards more efficient succinate production. The mutant had four functional mutations under the conditions investigated: increased expression of a succinate exporter (DcuC), deletion of a succinate importer (Dct), deletion of succinate dehydrogenase (SUCDH) and expression of a PEP carboxylase (PPC) with increased capacity due to a point mutation. The steady-state and dynamic patterns of the intracellular metabolite levels and fluxes in response to changes were used to locate the quantitative differences in the physiology/metabolism of the mutant strain. Unexpectedly the mutant had a higher energy efficiency, indicated by a much lower rate of oxygen consumption, under glucose-limited conditions, caused by the deletion of the transcription factors IclR and ArcA. Furthermore the mutant had a much lower uptake capacity for succinate (26-fold) and oxygen (17-fold under succinate excess) compared to the wild-type strain. The mutant strain produced 7.9 mmol.CmolX(-1).h(-1) succinate during chemostat cultivation, showing that the choice of the applied genetic modifications was a successful strategy. Furthermore, the applied genetic modifications resulted in multiple large changes in metabolite levels (FBP, pyruvate, 6PG, NAD(+) /NADH ratio, α-ketogluarate) corresponding to large changes in fluxes. Compared to the wild-type a considerable flux shift occurred from the tricarboxylic acid (TCA) cycle to the oxidative part of the pentose phosphate pathway, including an inversion of the pyruvate kinase flux. The mutant responded very differently to excess of succinate, with a remarkable possible reversal of the TCA cycle. The mutant and the wild-type both showed homeostatic behaviour with respect to the energy charge. In contrast, large changes in redox ratios (NAD(+) /NADH) occurred in the wild-type, while the mutant showed even larger changes. This large redox change can be associated to the reversal of flux directions. The observed large flexibility in the central metabolism following genetic (deletions) and environmental (substrate excess) perturbations of the mutant, indicates that introducing a more efficient succinate exporter could result in an even higher succinate production rate.

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Saccharomyces cerevisiae: a potential host for carboxylic acid production from lignocellulosic feedstock?

Cited by 20 publications

References 142 publications

Production of valuable compounds by molds and yeasts

Production of valuable compounds by molds and yeasts

Exploring the potential of the glycerol-3-phosphate dehydrogenase 2 (GPD2) promoter for recombinant gene expression in Saccharomyces cerevisiae

Comparative fluxome and metabolome analysis for overproduction of succinate in Escherichia coli

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