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Systems-based Saccharomyces cerevisiae strain design for improved squalene synthesis.

Kalaivani, P. and Punil Kumar, H. N. and Sarma, Mutturi (2019) Systems-based Saccharomyces cerevisiae strain design for improved squalene synthesis. Biochemical Engineering Journal, 148. pp. 37-45. ISSN 1369-703X

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Constraint-based flux balance analysis of S. cerevisiae has led to the identification of a novel gene deletion targets, LYS1 and ADK1, for enhancement of squalene flux. LYS1 deletion resulted in 2-fold improvement in squalene when compared to reference strain BY4741 with a maximum yield of 33.1 mg/g DCW. A double mutant of ADK1 and LYS1 genes has increased the squalene yield to 38 mg/g DW which is 2.38-fold higher over the control strain. Furthermore, single copies of tHMG1 and POS5 (with mitochondrial signal sequence) genes have been integrated into this double mutant in order to enhance the precursor pool and the cofactor regeneration capacity, respectively, for enhanced squalene synthesis. The improved strain, SK22 has resulted in squalene yield of 65 mg/g DW which is 4-folds higher than the control strain. Finally, the engineered strain was cultivated in a bioreactor using fed-batch strategy to improve the titer and productivity of squalene. Exponential feeding (open-loop strategy) using high residual glucose (~40-60 g/L) has increased the squalene titer to a maximum of 1.9 g/L with a yield of 0.15 g/g DCW, which is several folds higher than the shake-flask results. Redirecting the lysine synthesis by external supplementation could potentially improve squalene flux in S. cerevisiae.

Item Type: Article
Uncontrolled Keywords: Squalene; S. cerevisiae; genome-scale model; LYS1; Fed-batch
Subjects: 500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 24 Organic Chemistry
500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 19 Yeast
Divisions: Food Microbiology
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 31 May 2019 04:11
Last Modified: 31 May 2019 04:11
URI: http://ir.cftri.com/id/eprint/14094

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