In silico target-based strain engineering of Saccharomyces cerevisiae for terpene precursor improvement

Kalaivani, Paramasivan and Aneesha, Abdulla and Nabarupa, Gupta and Sarma, Mutturi (2022) In silico target-based strain engineering of Saccharomyces cerevisiae for terpene precursor improvement. Integrative Biology, 14. pp. 25-36.

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Abstract

Systems-based metabolic engineering enables cells to enhance product formation by predicting gene knockout and overexpression targets using modeling tools. FOCuS, a novel metaheuristic tool, was used to predict flux improvement targets in terpenoid pathway using the genome-scale model of Saccharomyces cerevisiae, iMM904. Some of the key knockout target predicted includes LYS1, GAP1, AAT1, AAT2, TH17, KGD-m, MET14, PDC1 and ACO1. It was also observed that the knockout reactions belonged either to fatty acid biosynthesis, amino acid synthesis pathways or nucleotide biosynthesis pathways. Similarly, overexpression targets such as PFK1, FBA1, ZWF1, TDH1, PYC1, ALD6, TPI1, PDX1 and ENO1 were established using three different existing gene amplification algorithms. Most of the overexpression targets belonged to glycolytic and pentose phosphate pathways. Each of these targets had plausible role for improving flux toward sterol pathway and were seemingly not artifacts. Moreover, an in vitro study as validation was carried with overexpression of ALD6 and TPI1. It was found that there was an increase in squalene synthesis by 2.23- and 4.24- folds, respectively, when compared with control. In general, the rationale for predicting these in silico targets was attributed to either increasing the acetyl-CoA precursor pool or regeneration of NADPH, which increase the sterol pathway flux.

Item Type:	Article
Uncontrolled Keywords:	in silico analysis, genome-scale model, knockout, overexpression, S. cerevisiae
Subjects:	600 Technology > 08 Food technology > 29 Microbiological food > 02 Fungi
Divisions:	Food Microbiology
Depositing User:	Somashekar K S
Date Deposited:	18 Dec 2025 11:06
Last Modified:	18 Dec 2025 11:06
URI:	http://ir.cftri.res.in/id/eprint/20225

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