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Genome‐scale metabolic modeling and in silico analysis of lipid accumulating yeast Candida tropicalis for dicarboxylic acid production
Author(s) -
Mishra Pranjul,
Park GyuYeon,
Lakshmanan Meiyappan,
Lee HeeSeok,
Lee Hongweon,
Chang Matthew Wook,
Ching Chi Bun,
Ahn Jungoh,
Lee DongYup
Publication year - 2016
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.25955
Subject(s) - candida tropicalis , biochemistry , biology , in silico , yeast , saccharomyces cerevisiae , metabolic pathway , metabolic flux analysis , flux (metallurgy) , metabolic engineering , flux balance analysis , pentose phosphate pathway , metabolic network , lipogenesis , lipid metabolism , citric acid cycle , fatty acid , metabolism , glycolysis , enzyme , chemistry , gene , organic chemistry
Recently, the bio‐production of α,ω‐dicarboxylic acids (DCAs) has gained significant attention, which potentially leads to the replacement of the conventional petroleum‐based products. In this regard, the lipid accumulating yeast Candida tropicalis , has been recognized as a promising microbial host for DCA biosynthesis: it possess the unique ω‐oxidation pathway where the terminal carbon of α‐fatty acids is oxidized to form DCAs with varying chain lengths. However, despite such industrial importance, its cellular physiology and lipid accumulation capability remain largely uncharacterized. Thus, it is imperative to better understand the metabolic behavior of this lipogenic yeast, which could be achieved by a systems biological approach. To this end, herein, we reconstructed the genome‐scale metabolic model of C. tropicalis , i CT646, accounting for 646 unique genes, 945 metabolic reactions, and 712 metabolites. Initially, the comparative network analysis of i CT646 with other yeasts revealed several distinctive metabolic reactions, mainly within the amino acid and lipid metabolism including the ω‐oxidation pathway. Constraints‐based flux analysis was, then, employed to predict the in silico growth rates of C. tropicalis which are highly consistent with the cellular phenotype observed in glucose and xylose minimal media chemostat cultures. Subsequently, the lipid accumulation capability of C. tropicalis was explored in comparison with Saccharomyces cerevisiae , indicating that the formation of “citrate pyruvate cycle” is essential to the lipid accumulation in oleaginous yeasts. The in silico flux analysis also highlighted the enhanced ability of pentose phosphate pathway as NADPH source rather than malic enzyme during lipogenesis. Finally, i CT646 was successfully utilized to highlight the key directions of C. tropicalis strain design for the whole cell biotransformation application to produce long‐chain DCAs from alkanes. Biotechnol. Bioeng. 2016;113: 1993–2004. © 2016 Wiley Periodicals, Inc.