Development of spatiotemporal model of growth and proliferation in fungi with kinetics of intracellular metabolism

Filamentous fungi are important hosts of industrial biotechnology. Yet, the production capacity suffers from the fungal morphology limitations. While the filamentous form is appropriate for production, in particular secreted products, pellet form is better suited for growth. By solely producing, adequate product levels cannot be obtained, as critical biomass is also needed, yet by solely growing, product yield would be low, especially for non-growth associated products. As a result, optimization of pellet or filamentous form in fungi became an important topic for biotechnological industry. S.cerevisiae existing in pellet or the intermediate form pseudohypha has long being studied for optimizing the suitable form for industrial fungi. To better understand, the trade-off between growth and production a spatio-temporal model (changing with time and space) has been developed taking into account simplified central metabolism of fungi. In doing so, pseudohyphal growth in solid state fermentation by S. cerevisiae was mimicked. To do so, general mass balances has been set up to describe how the cells grow and proliferates over time and space using partial differential equations. The resulting PDE has been solved using method of lines, discretizing space in two dimensions. The model takes growth as a function of intracellular ergosterol levels, thereby taking into account underlying metabolism, via mevalonate and ergosterol pathways starting from acetate. The acetate production has been linked to glucose representing a highly simplified form of central metabolism. The model could be used to study to understand how pathogenic fungi proliferates, and attack other cells, how the kinetics of intracellular reactions effect the phenotype, and the trade-off between growth and production in terms of distribution of energy among different cellular processes.