Modeling and optimization of lipid accumulation by Yarrowia lipolytica from glucose under nitrogen depletion conditions

Abstract

Oleaginous yeasts have been seen as a feasible alternative to produce the precursors of biodiesel due to their capacity to accumulate lipids as triacylglycerol having profiles with high content of unsaturated fatty acids. The yeast Yarrowia lipolytica is a promising microorganism that can produce lipids under nitrogen depletion conditions and excess of the carbon source. However, under these conditions, this yeast also produces citric acid (overflow metabolism) decreasing lipid productivity. This work presents two mathematical models for lipid production by Y. lipolytica from glucose. The first model is based on Monod and inhibition kinetics, and the second one is based on the Droop quota model approach, which is extended to yeast. The two models showed good agreements with the experimental data used for calibration and validation. The quota based model presented a better description of the dynamics of nitrogen and glucose dynamics leading to a good management of N/C ratio which makes this model interesting for control purposes. Then, quota model was used to evaluate, by means of simulation, a scenario for optimizing lipid productivity and lipid content. For that, a control strategy was designed by approximating the flow rates of glucose and nitrogen with piecewise linear functions. Simulation results achieved productivity of 0.95 g L hr and lipid content fraction of 0.23 g g , which indicates that this strategy is a promising alternative for the optimization of lipid production.

Partitioning metabolism between growth and product synthesis for coordinated production of wax esters in Acinetobacter baylyi ADP1

“…Such conditions inevitably lead to a trade‐off between biomass growth and lipid production. Various strategies to overcome this issue reduce the overall C/C yield and productivity, but can also induce growth inhibition and synthesis of overflow metabolites (Robles‐Rodríguez et al, 2018). To address the unfavorable effects of the high C/N ratio, various approaches of metabolic engineering ranging from gene knock‐outs, expression of nonnative enzymes, engineering redox metabolism, regulation of gene expression, and rewiring pathways have been proposed (Ajjawi et al, 2017; Lazar et al, 2018; Lehtinen et al, 2018; Liang & Jiang, 2013; Santala et al, 2011; Xu et al, 2016).…”

Lipid Production from Crude Glycerol by Newly Isolated Oleaginous Yeasts: Strain Selection, Molecular Identification and Fatty Acid Analysis

“…Yeast isolates were not utilized glycerol completely. It was thought that the accumulated lipids in the yeast cells were not used for lipid-free biomass synthesis because yeasts do not use their stored lipids before the run out of extracellular carbon supply [27,28,29].…”

Synthetic Biology Applied to Carbon Conservative and Carbon Dioxide Recycling Pathways

“…In addition, while NOG is redox neutral, the rGS pathway results in the net production of one NADH and one reduced quinone per glucose ( Table 1). This indicates that rGS is more energetically efficient than NOG which could be an advantage with respect to the production of acetyl-CoA derived products such as isoprenoids, fatty acids, long chain alcohols as they required reduced power and ATP (Tabata and Hashimoto, 2004;Kondo et al, 2012;Robles-Rodriguez et al, 2018).…”