Genome-scale metabolic modeling and In silico analysis of lipid accumulating yeast Candida tropicalis for dicarboxylic acid production

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Title
Genome-scale metabolic modeling and In silico analysis of lipid accumulating yeast Candida tropicalis for dicarboxylic acid production
Author(s)
P Mishra; Gyu-Yeon Park; M Lakshmanan; H S Lee; Hong-Weon Lee; M W Chang; C B Ching; Jungoh Ahn; D Y Lee
Bibliographic Citation
Biotechnology and Bioengineering, vol. 113, pp. 1993-2004
Publication Year
2016
Abstract
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, iCT646, accounting for 646 unique genes, 945 metabolic reactions, and 712 metabolites. Initially, the comparative network analysis of iCT646 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, iCT646 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.
Keyword
Candida tropicalisdicarboxylic acidgenome-scale metabolic modellipid accumulating yeastssystems biology
ISSN
0006-3592
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/bit.25955
Type
Article
Appears in Collections:
Division of Bio Technology Innovation > 1. Journal Articles
Division of Bio Technology Innovation > BioProcess Engineering Center > 1. Journal Articles
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