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Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation

Gonzalez-Ramos, D. (author), Van den Broek, M. (author), Van Maris, A.J.A. (author), Pronk, J.T. (author), Daran, J.M.G. (author)

Background n-Butanol and isobutanol produced from biomass-derived sugars are promising renewable transport fuels and solvents. Saccharomyces cerevisiae has been engineered for butanol production, but its high butanol sensitivity poses an upper limit to product titers that can be reached by further pathway engineering. A better understanding of...

journal article 2013

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Carbon dioxide fixation by Calvin-Cycle enzymes improves ethanol yield in yeast

Guadalupe-Medina, V. (author), Wisselink, H.W. (author), Luttik, M.A.H. (author), De Hulster, E. (author), Daran, J.M. (author), Pronk, J.T. (author), Van Maris, A.J.A. (author)

Background Redox-cofactor balancing constrains product yields in anaerobic fermentation processes. This challenge is exemplified by the formation of glycerol as major by-product in yeast-based bioethanol production, which is a direct consequence of the need to reoxidize excess NADH and causes a loss of conversion efficiency. Enabling the use of...

journal article 2013

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Growth-rate dependency of de novo resveratrol production in chemostat cultures of an engineered Saccharomyces cerevisiae strain

Vos, T. (author), De la Torre Cortes, P. (author), Van Gulik, W.M. (author), Pronk, J.T. (author), Daran-Lapujade, P.A.S. (author)

Introduction: Saccharomyces cerevisiae has become a popular host for production of non-native compounds. The metabolic pathways involved generally require a net input of energy. To maximize the ATP yield on sugar in S. cerevisiae, industrial cultivation is typically performed in aerobic, sugar-limited fed-batch reactors which, due to constraints...

journal article 2015

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An internal deletion in MTH1 enables growth on glucose of pyruvate-decarboxylase negative, non-fermentative Saccharomyces cerevisiae

Oud, B. (author), Flores, C.L. (author), Gancedo, C. (author), Zhang, X. (author), Trueheart, J. (author), Daran, J.M. (author), Pronk, J.T. (author), Van Maris, A.J.A. (author)

Background Pyruvate-decarboxylase negative (Pdc-) strains of Saccharomyces cerevisiae combine the robustness and high glycolytic capacity of this yeast with the absence of alcoholic fermentation. This makes Pdc-S. cerevisiae an interesting platform for efficient conversion of glucose towards pyruvate-derived products without formation of ethanol...

journal article 2012

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One-step assembly and targeted integration of multigene constructs assisted by the I-SceI meganuclease in Saccharomyces cerevisiae

Kuijpers, N.G.A. (author), Chroumpi, S. (author), Vos, T. (author), Solis-Escalante, D. (author), Bosman, D. (author), Pronk, J.T. (author), Daran, J.G. (author), Daran-Lapujade, P.A.S. (author)

In vivo assembly of overlapping fragments by homologous recombination in Saccharomyces cerevisiae is a powerful method to engineer large DNA constructs. Whereas most in vivo assembly methods reported to date result in circular vectors, stable integrated constructs are often preferred for metabolic engineering as they are required for large-scale...

journal article 2013

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Functional characterization of the oxaloacetase encoding gene and elimination of oxalate formation in the β-lactam producer Penicillium chrysogenum

Daran, J.M. (author), Pronk, J.T. (author), Driessen, A.J.M. (author), Nijland, J.G. (author), Lamboo, F. (author), Puig-Martinez, M. (author), Veiga, T. (author), Gombert, A.K. (author)

Penicillium chrysogenum is widely used as an industrial antibiotic producer, in particular in the synthesis of ß-lactam antibiotics such as penicillins and cephalosporins. In industrial processes, oxalic acid formation leads to reduced product yields. Moreover, precipitation of calcium oxalate complicates product recovery. We observed oxalate...

journal article 2011

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Genome duplication and mutations in ACE2 cause multicellular, fast-sedimenting phenotypes in evolved Saccharomyces cerevisiae

Oud, B. (author), Guadalupe-Medina, V. (author), Nijkamp, J.F. (author), De Ridder, D. (author), Pronk, J.T. (author), Van Maris, A.J.A. (author), Daran, J.G. (author)

Laboratory evolution of the yeast Saccharomyces cerevisiae in bioreactor batch cultures yielded variants that grow as multicellular, fast-sedimenting clusters. Knowledge of the molecular basis of this phenomenon may contribute to the understanding of natural evolution of multicellularity and to manipulating cell sedimentation in laboratory and...

journal article 2013

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Metabolic engineering of ?-oxidation in Penicillium chrysogenum for improved semi-synthetic cephalosporin biosynthesis

Veiga, T. (author), Gombert, A.K. (author), Landes, N. (author), Verhoeven, M.D. (author), Kiel, J.A.K.W. (author), Krikken, A. (author), Nijland, J.G. (author), Touw, H. (author), Luttik, M.A.H. (author), Van der Toorn, J.C. (author), Driessen, A.J.M. (author), Bovenberg, R.A.L. (author), Van den Berg, M.A. (author), Van der Klei, I.J. (author), Pronk, J.T. (author), Daran, J.M. (author)

Industrial production of semi-synthetic cephalosporins by Penicillium chrysogenum requires supplementation of the growth media with the side-chain precursor adipic acid. In glucose-limited chemostat cultures of P. chrysogenum, up to 88% of the consumed adipic acid was not recovered in cephalosporin-related products, but used as an additional...

journal article 2012

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De novo production of the flavonoid naringenin in engineered Saccharomyces cerevisiae

Koopman, F.W. (author), Beekwilder, J. (author), Crimi, B. (author), Van Houwelingen, A. (author), Hall, R.D. (author), Bosch, D. (author), Van Maris, A.J.A. (author), Pronk, J.T. (author), Daran, J.M. (author)

Background Flavonoids comprise a large family of secondary plant metabolic intermediates that exhibit a wide variety of antioxidant and human health-related properties. Plant production of flavonoids is limited by the low productivity and the complexity of the recovered flavonoids. Thus to overcome these limitations, metabolic engineering of...

journal article 2012

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Pyruvate Metabolism in Saccharomyces cerevisiae

Pronk, J.T. (author), Steensma, H.Y. (author), van Dijken, J.P. (author)

journal article 1996

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The Esiac-10 Algebraic Computer: A theoretical decomposition by the Historic Collection

Pronk, C. (author), Trimp, P.J. (author)

A description of the working pricciples of the Esiac-10 Algebraic Computer

journal article 2022

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Evolutionary engineering in chemostat cultures for improved maltotriose fermentation kinetics in saccharomyces pastorianus lager brewing yeast

Brickwedde, A. (author), van den Broek, M.A. (author), Geertman, Jan Maarten A. (author), Magalhães, Frederico (author), Kuijpers, Niels G.A. (author), Gibson, Brian (author), Pronk, J.T. (author), Daran, J.G. (author)

The lager brewing yeast Saccharomyces pastorianus, an interspecies hybrid of S. eubayanus and S. cerevisiae, ferments maltotriose, maltose, sucrose, glucose and fructose in wort to ethanol and carbon dioxide. Complete and timely conversion ("attenuation") of maltotriose by industrial S. pastorianus strains is a key requirement for process...

journal article 2017

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Elimination of sucrose transport and hydrolysis in Saccharomyces cerevisiae: a platform strain for engineering sucrose metabolism

Marques, W.L. (author), Mans, R. (author), Marella, Eko Roy (author), Cordeiro, Rosa Lorizolla (author), van den Broek, M.A. (author), Daran, J.G. (author), Pronk, J.T. (author), Gombert, Andreas K. (author), van Maris, A.J.A. (author)

Many relevant options to improve efficacy and kinetics of sucrose metabolism in Saccharomyces cerevisiae and, thereby, the economics of sucrose-based processes remain to be investigated. An essential first step is to identify all native sucrose-hydrolysing enzymes and sucrose transporters in this yeast, including those that can be activated...

journal article 2017

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Saccharomyces cerevisiae strains tor second-generation ethanol production: from academie exploration to industrial implementation

Jansen, Mickel L.A. (author), Bracher, J.M. (author), Papapetridis, I. (author), Verhoeven, M.D. (author), de Bruijn, J.A. (author), de Waal, P. (author), van Maris, A.J.A. (author), Klaassen, P (author), Pronk, J.T. (author)

The recent start-up of several full-scale ‘second generation’ ethanol plants marks a major milestone in the development of Saccharomyces cerevisiae strains for fermentation of lignocellulosic hydrolysates of agricultural residues and energy crops. After a discussion of the challenges that these novel industrial contexts impose on yeast strains,...

journal article 2017

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Pathway engineering strategies for improved product yield in yeast-based industrial ethanol production

van Aalst, A.C.A. (author), de Valk, S.C. (author), van Gulik, W.M. (author), Jansen, Mickel L.A. (author), Pronk, J.T. (author), Mans, R. (author)

Product yield on carbohydrate feedstocks is a key performance indicator for industrial ethanol production with the yeast Saccharomyces cerevisiae. This paper reviews pathway engineering strategies for improving ethanol yield on glucose and/or sucrose in anaerobic cultures of this yeast by altering the ratio of ethanol production, yeast growth...

journal article 2022

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Engineering the thermotolerant industrial yeast Kluyveromyces marxianus for anaerobic growth

Dekker, W.J.C. (author), Ortiz Merino, R.A. (author), Kaljouw, Astrid (author), Battjes, Julius (author), Wiering, Frank W. (author), Mooiman, C. (author), de la Torre, P. (author), Pronk, J.T. (author)

Current large-scale, anaerobic industrial processes for ethanol production from renewable carbohydrates predominantly rely on the mesophilic yeast Saccharomyces cerevisiae. Use of thermotolerant, facultatively fermentative yeasts such as Kluyveromyces marxianus could confer significant economic benefits. However, in contrast to S. cerevisiae,...

journal article 2021

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Engineering heterologous molybdenum-cofactor-biosynthesis and nitrate-assimilation pathways enables nitrate utilization by Saccharomyces cerevisiae

Perli, T. (author), van der Vorm, Daan N.A. (author), Wassink, Mats (author), van den Broek, M.A. (author), Pronk, J.T. (author), Daran, J.G. (author)

Metabolic capabilities of cells are not only defined by their repertoire of enzymes and metabolites, but also by availability of enzyme cofactors. The molybdenum cofactor (Moco) is widespread among eukaryotes but absent from the industrial yeast Saccharomyces cerevisiae. No less than 50 Moco-dependent enzymes covering over 30 catalytic...

journal article 2021

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Co-cultivation of Saccharomyces cerevisiae strains combines advantages of different metabolic engineering strategies for improved ethanol yield

van Aalst, A.C.A. (author), van der Meulen, Igor S. (author), Jansen, Mickel L.A. (author), Mans, R. (author), Pronk, J.T. (author)

Glycerol is the major organic byproduct of industrial ethanol production with the yeast Saccharomyces cerevisiae. Improved ethanol yields have been achieved with engineered S. cerevisiae strains in which heterologous pathways replace glycerol formation as the predominant mechanism for anaerobic re-oxidation of surplus NADH generated in...

journal article 2023

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Replacement of the initial steps of ethanol metabolism in Saccharomyces cerevisiae by ATP-independent acetylating acetaldehyde dehydrogenase

Kozak, B.U. (author), Rossum, Harmen M. (author), Niemeijer, M.S. (author), van Dijk, M. (author), Benjamin, Kirsten (author), Wu, Liang (author), Daran, J.G. (author), Pronk, J.T. (author), van Maris, A.J.A. (author)

In Saccharomyces cerevisiae ethanol dissimilation is initiated by its oxidation and activation to cytosolic acetyl-CoA. The associated consumption of ATP strongly limits yields of biomass and acetyl-CoA-derived products. Here, we explore the implementation of an ATP-independent pathway for acetyl-CoA synthesis from ethanol that, in theory,...

journal article 2016

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A new laboratory evolution approach to select for constitutive acetic acid tolerance in Saccharomyces cerevisiae and identification of causal mutations

Gonzalez Ramos, D. (author), Gorter de Vries, A.R. (author), Grijseels, Sietske S. (author), van Berkum, M.C. (author), Swinnen, Steve (author), van den Broek, M.A. (author), Nevoigt, Elke (author), Daran, J.G. (author), Pronk, J.T. (author), van Maris, A.J.A. (author)

Background: Acetic acid, released during hydrolysis of lignocellulosic feedstocks for second generation bioethanol production, inhibits yeast growth and alcoholic fermentation. Yeast biomass generated in a propagation step that precedes ethanol production should therefore express a high and constitutive level of acetic acid tolerance before...

journal article 2016