Abstract
The genome-scale metabolic model of a lipid-overproducing strain of Mucor circinelloides WJ11 was developed. The model (iNI1159) contained 1,159 genes, 648 EC numbers, 1,537 metabolites, and 1,355 metabolic reactions, which were localized in different compartments of the cell. Using flux balance analysis (FBA), the iNI1159 model was validated by predicting the specific growth rate. The metabolic traits investigated by phenotypic phase plane analysis (PhPP) showed a relationship between the nutrient uptake rate, cell growth, and the triacylglycerol production rate, demonstrating the strength of the model. A putative set of metabolic reactions affecting the lipid-accumulation process was identified when the metabolic flux distributions under nitrogen-limited conditions were altered by performing fast flux variability analysis (fastFVA) and relative flux change. Comparative analysis of the metabolic models of the lipid-overproducing strain WJ11 (iNI1159) and the reference strain CBS277.49 (iWV1213) using both fastFVA and coordinate hit-and-run with rounding (CHRR) showed that the flux distributions between these two models were significantly different. Notably, a higher flux distribution through lipid metabolisms such as lanosterol, zymosterol, glycerolipid and fatty acids biosynthesis in iNI1159 was observed, leading to an increased lipid production when compared to iWV1213. In contrast, iWV1213 exhibited a higher flux distribution across carbohydrate and amino acid metabolisms and thus generated a high flux for biomass production. This study demonstrated that iNI1159 is an effective predictive tool for the pathway engineering of oleaginous strains for the production of diversified oleochemicals with industrial relevance.
Highlights
Due to the world population growth and the industrial revolution, the value addition of agricultural materials and residues has been attributed to the sustainable production of biobased products
The developed genome-scale metabolic model (GEM) of the M. circinelloides WJ11 strain was achieved. It consisted of 1,159 genes (10.6% of total genes in M. circinelloides WJ11 genome), 648 EC numbers, 1,537 metabolites and 1,355 metabolic reactions, which were distributed into five compartments of the cell, namely, the mitochondria, extracellular
The developed iNI1159 empowering the prediction of biomass and lipid production of M. circinelloides WJ11 could be exploited to explain its metabolic phenotypes through changes in metabolic flux distribution
Summary
Due to the world population growth and the industrial revolution, the value addition of agricultural materials and residues has been attributed to the sustainable production of biobased products. The dedicated biobased oleochemicals and functional lipids with industrial applications (Salimon, Salih & Yousif, 2012; Vanhercke et al, 2013; Hatti-Kaul et al, 2007) are of a great interest. Oleaginous microorganisms are currently of interest as cell chassis for pathway manipulation because they exhibit phenotypes with advantages in the cultivation process and lipid production. Mucor circinelloides is a well-known oleaginous fungus that accumulates lipids at high levels, under certain culture conditions (Xia et al, 2011). M. circinelloides is capable of synthesizing the nutritionally important polyunsaturated fatty acid (PUFA), γ-linolenic acid (GLA, C18:3 n-6; cis 6, 9, 12-octadecatrienoic acid), which has beneficial effects on human and animal health (Zurier, 1998)
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