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Predicting the influence of combined oxygen and glucose gradients based on scale-down and modelling approaches for the scale-up of penicillin fermentations

Jánoska, A. (author), Buijs, Joran (author), van Gulik, W.M. (author)

In large scale fermentors the cultivated cells are exposed to dynamic changes in the nutrient concentrations due to imperfect mixing. Based on the characterization of these nutrient gradients in space and time, a rational scale down design can be obtained. This study focuses on the combined gradients of dissolved sugar and oxygen...

journal article 2023

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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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Influence of oxygen concentration on the metabolism of Penicillium chrysogenum

Jánoska, A. (author), Verheijen, Jelle J. (author), Tang, W. (author), Lee, Queenie (author), Sikkema, Baukje (author), van Gulik, W.M. (author)

In large-scale bioreactors, there is often insufficient mixing and as a consequence, cells experience uneven substrate and oxygen levels that influence product formation. In this study, the influence of dissolved oxygen (DO) gradients on the primary and secondary metabolism of a high producing industrial strain of Penicillium chrysogenum was...

journal article 2022

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Monitoring Intracellular Metabolite Dynamics in Saccharomyces cerevisiae during Industrially Relevant Famine Stimuli

Minden, Steven (author), Aniolek, Maria (author), Sarkizi Shams Hajian, Christopher (author), Teleki, Attila (author), Zerrer, Tobias (author), Delvigne, Frank (author), van Gulik, W.M. (author), Deshmukh, Amit (author), Noorman, H.J. (author), Takors, Ralf (author)

Carbon limitation is a common feeding strategy in bioprocesses to enable an efficient microbiological conversion of a substrate to a product. However, industrial settings inherently promote mixing insufficiencies, creating zones of famine conditions. Cells frequently traveling through such regions repeatedly experience substrate shortages and...

journal article 2022

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Genome-wide effect of non-optimal temperatures under anaerobic conditions on gene expression in Saccharomyces cerevisiae

García-Ríos, Estéfani (author), Alonso-del-Real, Javier (author), Lip, K.Y.F. (author), Pinheiro, Tania (author), Teixeira, José (author), van Gulik, W.M. (author), Domingues, Lucília (author), Querol, Amparo (author), Guillamón, José Manuel (author)

Understanding of thermal adaptation mechanisms in yeast is crucial to develop better-adapted strains to industrial processes, providing more economical and sustainable products. We have analyzed the transcriptomic responses of three Saccharomyces cerevisiae strains, a commercial wine strain, ADY5, a laboratory strain, CEN.PK113-7D and a...

journal article 2022

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Uncoupling growth and succinic acid production in an industrial Saccharomyces cerevisiae strain

Liu, Y. (author), Esen, Osman (author), Pronk, J.T. (author), van Gulik, W.M. (author)

This study explores the relation between biomass-specific succinic acid (SA) production rate and specific growth rate of an engineered industrial strain of Saccharomyces cerevisiae, with the aim to investigate the extent to which growth and product formation can be uncoupled. Ammonium-limited aerobic chemostat and retentostat cultures were...

journal article 2021

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Fed-Batch Droplet Nanobioreactor for Controlled Growth of Cyberlindnera (Pichia) jadinii: A Proof-Of-Concept Demonstration

Totlani, K. (author), Wang, Yen Chieh (author), Bisschops, Maxime (author), de Riese, Thorben (author), Kreutzer, M.T. (author), van Gulik, W.M. (author), van Steijn, V. (author)

A key bottleneck in bioprocess development is that state-of-the-art tools used for screening of cells and optimization of cultivation conditions do not represent the conditions enforced at industrial scale. At industrial scale, cell growth is strictly controlled (“fed-batch”) to optimize the metabolites produced by the cells. In contrast,...

journal article 2021

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A possible influence of extracellular polysaccharides on the analysis of intracellular metabolites from Trichoderma harzianum grown under carbon-limited conditions

Gelain, L. (author), Geraldo da Cruz Pradella, José (author), Carvalho da Costa, Aline (author), van der Wielen, L.A.M. (author), van Gulik, W.M. (author)

Intracellular metabolites were evaluated during the continuous growth of Trichoderma harzianum P49P11 under carbon-limited conditions. Four different conditions in duplicate were investigated (10 and 20 g/L of glucose, 5.26/5.26 g/L of fructose/glucose and 10 g/L of sucrose in the feed). Differences in the values of some specific...

journal article 2021

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Differential proteomic analysis by SWATH-MS unravels the most dominant mechanisms underlying yeast adaptation to non-optimal temperatures under anaerobic conditions

Pinheiro, Tânia (author), Lip, K.Y.F. (author), García-Ríos, Estéfani (author), Querol, Amparo (author), Teixeira, José (author), van Gulik, W.M. (author), Guillamón, José Manuel (author), Domingues, Lucília (author)

Elucidation of temperature tolerance mechanisms in yeast is essential for enhancing cellular robustness of strains, providing more economically and sustainable processes. We investigated the differential responses of three distinct Saccharomyces cerevisiae strains, an industrial wine strain, ADY5, a laboratory strain, CEN.PK113-7D and an...

journal article 2020

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Triplet-blockaded Josephson supercurrent in double quantum dots

Bouman, D. (author), van Gulik, R.J.J. (author), Steffensen, Gorm (author), Pataki, Dávid (author), Boross, Péter (author), Krogstrup, Peter (author), Nygård, Jesper (author), Paaske, Jens (author), Pályi, András (author), Geresdi, A. (author)

Serial double quantum dots created in semiconductor nanostructures provide a versatile platform for investigating two-electron spin quantum states, which can be tuned by electrostatic gating and an external magnetic field. In this Rapid Communication, we directly measure the supercurrent reversal between adjacent charge states of an InAs...

journal article 2020

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Scalable microfluidic droplet on-demand generator for non-steady operation of droplet-based assays

Totlani, K. (author), Hurkmans, Jan Willem (author), van Gulik, W.M. (author), Kreutzer, M.T. (author), van Steijn, V. (author)

We developed a microfluidic droplet on-demand (DoD) generator that enables the production of droplets with a volume solely governed by the geometry of the generator for a range of operating conditions. The prime reason to develop this novel type of DoD generator is that its robustness in operation enables scale out and operation under non...

journal article 2020

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Selection and subsequent physiological characterization of industrial Saccharomyces cerevisiae strains during continuous growth at sub- and- supra optimal temperatures

Lip, K.Y.F. (author), García-Ríos, Estéfani (author), Costa, Carlos E. (author), Guillamón, José Manuel (author), Domingues, Lucília (author), Teixeira, José (author), van Gulik, W.M. (author)

A phenotypic screening of 12 industrial yeast strains and the well-studied laboratory strain CEN.PK113-7D at cultivation temperatures between 12 °C and 40 °C revealed significant differences in maximum growth rates and temperature tolerance. From those 12, two strains, one performing best at 12 °C and the other at 40 °C, plus the laboratory...

journal article 2020

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Analysis of the proteins secreted by Trichoderma harzianum P49P11 under carbon-limited conditions

Gelain, L. (author), Pabst, Martin (author), da Cruz Pradella, José Geraldo (author), da Costa, Aline Carvalho (author), van der Wielen, L.A.M. (author), van Gulik, W.M. (author)

The wild type strain Trichoderma harzianum was able to synthesize enzymes that can catalyse the hydrolysis of p-nitrophenyl-β-D-glucopyranoside (PNPGase) in glucose-limited chemostat cultures. Fructose/glucose and sucrose conditions provided low levels of PNPGase activity. To investigate whether under these conditions other enzymes were...

journal article 2020

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Mathematical modelling for the optimization of cellulase production using glycerol for cell growth and cellulose as the inducer substrate

Gelain, L. (author), van der Wielen, L.A.M. (author), van Gulik, W.M. (author), da Cruz Pradella, José Geraldo (author), Carvalho da Costa, Aline (author)

Cellulase production can be divided into two steps: growth stage; followed by an induction stage. To develop a mathematical model for the optimization of this strategy, two sets of experiments were performed in batch mode for parameter estimation. One set of experiments was performed to evaluate the influence of glycerol regarding cell growth...

journal article 2020

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Continuous production of enzymes under carbon-limited conditions by Trichoderma harzianum P49P11

Gelain, L. (author), Kingma, Esther (author), Geraldo da Cruz Pradella, José (author), Carvalho da Costa, Aline (author), van der Wielen, L.A.M. (author), van Gulik, W.M. (author)

Carbon-limited chemostat cultures were performed using different carbon sources (glucose, 10 and 20 g/L; sucrose, 10 g/L; fructose/glucose, 5.26/5.26 g/L; carboxymethyl cellulose, 10 g/L; and carboxymethyl cellulose/glucose, 5/5 g/L) to verify the capability of the wild type strain Trichoderma harzianum to produce extracellular enzymes. All...

journal article 2020

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Observation of the 4π-periodic Josephson effect in indium arsenide nanowires

Laroche, D. (author), Bouman, D. (author), van Woerkom, D.J. (author), Proutski, A. (author), Murthy, Chaitanya (author), Nayak, Chetan (author), van Gulik, R.J.J. (author), Kouwenhoven, Leo P. (author), Geresdi, A. (author)

Quantum computation by non-Abelian Majorana zero modes (MZMs) offers an approach to achieve fault tolerance by encoding quantum information in the non-local charge parity states of semiconductor nanowire networks in the topological superconductor regime. Thus far, experimental studies of MZMs chiefly relied on single electron tunneling...

journal article 2019

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Physiological responses of Saccharomyces cerevisiae to industrially relevant conditions: Slow growth, low pH, and high CO₂ levels

Hakkaart, X.D.V. (author), Liu, Y. (author), Hulst, Mandy (author), el Masoudi, Anissa (author), Peuscher, Eveline (author), Pronk, J.T. (author), van Gulik, W.M. (author), Daran-Lapujade, P.A.S. (author)

Engineered strains of Saccharomyces cerevisiae are used for industrial production of succinic acid. Optimal process conditions for dicarboxylic-acid yield and recovery include slow growth, low pH, and high CO₂. To quantify and understand how these process parameters affect yeast physiology, this study investigates individual and...

journal article 2019

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Comparison between dynamic gadoxetate-enhanced MRI and ^99m Tc-mebrofenin hepatobiliary scintigraphy with SPECT for quantitative assessment of liver function

Rassam, F. (author), Zhang, T. (author), Cieslak, K. P. (author), Lavini, C. (author), Stoker, J. (author), Bennink, R. J. (author), van Gulik, T. M. (author), van Vliet, L.J. (author), Runge, J. H. (author), Vos, F.M. (author)

Objectives: To compare Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) with ^99m Tc-mebrofenin hepatobiliary scintigraphy (HBS) as quantitative liver function tests for the preoperative assessment of patients undergoing liver resection. Methods: Patients undergoing liver surgery and preoperative assessment...

journal article 2019

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A pharmacokinetic model including arrival time for two inputs and compensating for varying applied flip-angle in dynamic gadoxetic acid-enhanced MR imaging

Zhang, T. (author), Runge, Jurgen H. (author), Lavini, Cristina (author), Stoker, Jaap (author), van Gulik, Thomas (author), Cieslak, Kasia P. (author), van Vliet, L.J. (author), Vos, F.M. (author)

Purpose Pharmacokinetic models facilitate assessment of properties of the micro-vascularization based on DCE-MRI data. However, accurate pharmacokinetic modeling in the liver is challenging since it has two vascular inputs and it is subject to large deformation and displacement due to respiration. Methods We propose an improved...

journal article 2019

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Quantitative Physiology of Non-Energy-Limited Retentostat Cultures of Saccharomyces cerevisiae at Near-Zero Specific Growth Rates

Liu, Y. (author), El Masoudi, Anissa (author), Pronk, J.T. (author), van Gulik, W.M. (author)

So far, the physiology of Saccharomyces cerevisiae at near-zero growth rates has been studied in retentostat cultures with a growth-limiting supply of the carbon and energy source. Despite its relevance in nature and industry, the near-zero growth physiology of S. cerevisiae under conditions where growth is limited by the supply of non-energy...

journal article 2019