Dynamic Interplay between O<sub>2</sub> Availability, Growth Rates, and the Transcriptome of <i>Yarrowia lipolytica</i>

Industrial-sized fermenters differ from the laboratory environment in which bioprocess development initially took place. One of the issues that can lead to reduced productivity on a large scale or even early termination of the process is the presence of bioreactor heterogeneities. This work proposes...

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Main Authors: Abraham A. J. Kerssemakers, Süleyman Øzmerih, Gürkan Sin, Suresh Sudarsan
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Fermentation
Subjects:
Online Access:https://www.mdpi.com/2311-5637/9/1/74
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author Abraham A. J. Kerssemakers
Süleyman Øzmerih
Gürkan Sin
Suresh Sudarsan
author_facet Abraham A. J. Kerssemakers
Süleyman Øzmerih
Gürkan Sin
Suresh Sudarsan
author_sort Abraham A. J. Kerssemakers
collection DOAJ
description Industrial-sized fermenters differ from the laboratory environment in which bioprocess development initially took place. One of the issues that can lead to reduced productivity on a large scale or even early termination of the process is the presence of bioreactor heterogeneities. This work proposes and adopts a design–build–test–learn-type workflow that estimates the substrate, oxygen, and resulting growth heterogeneities through a compartmental modelling approach and maps <i>Yarrowia lipolytica</i>-specific behavior in this relevant range of conditions. The results indicate that at a growth rate of 0.1 h<sup>−1</sup>, the largest simulated volume (90 m<sup>3</sup>) reached partial oxygen limitation. Throughout the fed-batch, the cells experienced dissolved oxygen values from 0 to 75% and grew at rates of 0 to 0.2 h<sup>−1</sup>. These simulated large-scale conditions were tested in small-scale cultivations, which elucidated a transcriptome with a strong downregulation of various transporter and central carbon metabolism genes during oxygen limitation. The relation between oxygen availability and differential gene expression was dynamic and did not show a simple on–off behavior. This indicates that <i>Y. lipolytica</i> can differentiate between different available oxygen concentrations and adjust its transcription accordingly. The workflow presented can be used for <i>Y. lipolytica</i>-based strain engineering, thereby accelerating bioprocess development.
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spelling doaj.art-7a8b26ac10a74a37819e734d28fde03c2023-11-30T22:11:08ZengMDPI AGFermentation2311-56372023-01-01917410.3390/fermentation9010074Dynamic Interplay between O<sub>2</sub> Availability, Growth Rates, and the Transcriptome of <i>Yarrowia lipolytica</i>Abraham A. J. Kerssemakers0Süleyman Øzmerih1Gürkan Sin2Suresh Sudarsan3The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2800 Kgs. Lyngby, DenmarkThe Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2800 Kgs. Lyngby, DenmarkProcess and Systems Engineering Research Center, Department of Chemical and Biochemical Engineering, Technical University of Denmark, DK-2800 Kgs. Lyngby, DenmarkThe Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2800 Kgs. Lyngby, DenmarkIndustrial-sized fermenters differ from the laboratory environment in which bioprocess development initially took place. One of the issues that can lead to reduced productivity on a large scale or even early termination of the process is the presence of bioreactor heterogeneities. This work proposes and adopts a design–build–test–learn-type workflow that estimates the substrate, oxygen, and resulting growth heterogeneities through a compartmental modelling approach and maps <i>Yarrowia lipolytica</i>-specific behavior in this relevant range of conditions. The results indicate that at a growth rate of 0.1 h<sup>−1</sup>, the largest simulated volume (90 m<sup>3</sup>) reached partial oxygen limitation. Throughout the fed-batch, the cells experienced dissolved oxygen values from 0 to 75% and grew at rates of 0 to 0.2 h<sup>−1</sup>. These simulated large-scale conditions were tested in small-scale cultivations, which elucidated a transcriptome with a strong downregulation of various transporter and central carbon metabolism genes during oxygen limitation. The relation between oxygen availability and differential gene expression was dynamic and did not show a simple on–off behavior. This indicates that <i>Y. lipolytica</i> can differentiate between different available oxygen concentrations and adjust its transcription accordingly. The workflow presented can be used for <i>Y. lipolytica</i>-based strain engineering, thereby accelerating bioprocess development.https://www.mdpi.com/2311-5637/9/1/74compartmental modellingmetabolic regimesoxygen limitationscale-downtranscriptome response
spellingShingle Abraham A. J. Kerssemakers
Süleyman Øzmerih
Gürkan Sin
Suresh Sudarsan
Dynamic Interplay between O<sub>2</sub> Availability, Growth Rates, and the Transcriptome of <i>Yarrowia lipolytica</i>
Fermentation
compartmental modelling
metabolic regimes
oxygen limitation
scale-down
transcriptome response
title Dynamic Interplay between O<sub>2</sub> Availability, Growth Rates, and the Transcriptome of <i>Yarrowia lipolytica</i>
title_full Dynamic Interplay between O<sub>2</sub> Availability, Growth Rates, and the Transcriptome of <i>Yarrowia lipolytica</i>
title_fullStr Dynamic Interplay between O<sub>2</sub> Availability, Growth Rates, and the Transcriptome of <i>Yarrowia lipolytica</i>
title_full_unstemmed Dynamic Interplay between O<sub>2</sub> Availability, Growth Rates, and the Transcriptome of <i>Yarrowia lipolytica</i>
title_short Dynamic Interplay between O<sub>2</sub> Availability, Growth Rates, and the Transcriptome of <i>Yarrowia lipolytica</i>
title_sort dynamic interplay between o sub 2 sub availability growth rates and the transcriptome of i yarrowia lipolytica i
topic compartmental modelling
metabolic regimes
oxygen limitation
scale-down
transcriptome response
url https://www.mdpi.com/2311-5637/9/1/74
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AT gurkansin dynamicinterplaybetweenosub2subavailabilitygrowthratesandthetranscriptomeofiyarrowialipolyticai
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