Inhibition kinetics of bio-based succinic acid production by the yeast Yarrowia lipolytica

Kinetic models that describe the fermentative SA production by the yeast Yarrowia lipolytica were developed for the first time. A modified Monod model considering both substrate and product inhibition based on shake flask experiments is proposed to describe the cell growth. Y. lipolytica tolerated up to 302.4 g/L glycerol, and significant decrease in SA yield and prolonged lag phase were observed with glycerol concentration above 212.0 g/L. Among the end-products investigated, acetic acid (AA) was found to have the most inhibitory effect on SA fermentation. The critical concentrations of SA and AA were 243.4 g/L and 57.9 g/L respectively. These demonstrated the greater potential of the yeast than bacterial SA producers. An unstructured model, based on a basic mass-balance of carbon, was used to describe substrate consumption, from which the cell maintenance coefficient tit, was estimated to be 0.118 g/(g h). The Luedeking-Piret model was applied to describe the accumulation of organic acids, with SA and AA production following a mixed-growth-associated pattern. The values of the growth-associated term of both SA (0.386 g/g-DCW) and AA (0.208 g/g-DCW) were much higher than those of the non-growth-associated term of SA (0.013 g/(g-DCW h)) and AA (0.010 g/(g-DCW h)) respectively, indicating these products were mainly formed in tandem with yeast growth. After optimisation and validation, the model simulations match the experimental observations well, enabling elucidation of the fermentation characteristics for Y. lipolytica possible. This paper provides key insights into the improvement of SA production and the modelling of inhibition kinetics.