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Lookup NU author(s): Dr Varun OjhaORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC. Our research aims to help industrial biotechnology develop a sustainable economy using green technology based on microorganisms and synthetic biology through two case studies that improve metabolic capacity in yeast models Yarrowia lipolytica (Y. lipolytica) and Saccharomyces cerevisiae (S. cerevisiae). We aim to increase the production capacity of beta-carotene (β-carotene) and succinic acid, which are among the highest market demands due to their versatile use in numerous consumer products. We performed simulations to identify in silico ranking of strains based on multiple objectives: the growth rate of yeast microorganisms, the number of used chromosomes, and the production capability of β-carotene (for Y. lipolytica) and succinate (for S. cerevisiae). Our multiobjective optimization methodology identified notable gene deletions by searching a vast solution space to highlight near-optimal strains on Pareto Fronts, balancing the above-cited three objectives. Moreover, preserving the metabolic constraints and the essential genes, this study produced robust results: seven significant strains of Y. lipolytica and seven strains of S. cerevisiae. We examined gene knockout to study the function of genes and pathways. In fact, by studying the frequently silenced genes, we found that when the GPH1 gene is knocked out in S. cerevisiae, the isocitrate lyase enzyme is activated, which converts the isocitrate into succinate. Our goals are to simplify and facilitate the in vitro processes. Hence, we present strains with the least possible number of knockout genes and solutions in which the genes are turned off on the same chromosome. Therefore, we present results where the constraints mentioned above are met, like the strains where only two genes are switched off and other strains where half of the knockout genes are on the same chromosome. This study offers solutions for developing an efficient in vitro mutagenesis for microorganisms and demonstrates the efficiency of multiobjective optimization in automatizing metabolic engineering processes.
Author(s): Amaradio MN, Ojha V, Jansen G, Gulisano M, Costanza J, Nicosia G
Publication type: Article
Publication status: Published
Journal: Biotechnology and Bioengineering
Year: 2022
Volume: 119
Issue: 7
Pages: 1890-1902
Print publication date: 01/07/2022
Online publication date: 13/04/2022
Acceptance date: 07/04/2022
Date deposited: 09/03/2023
ISSN (print): 0006-3592
ISSN (electronic): 1097-0290
Publisher: John Wiley and Sons Inc.
URL: https://doi.org/10.1002/bit.28103
DOI: 10.1002/bit.28103
PubMed id: 35419827
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