Dynamic flux balance analysis of batch fermentation: effect of genetic manipulations on ethanol production.

In silico optimization of bioethanol production from lignocellulosic biomasses is investigated by combining process systems engineering approach and systems biology approach. Lignocellulosic biomass is an attractive sustainable carbon source for fermentative production of bioethanol. For enhanced ethanol production, metabolic engineering of wild-type strains-that can metabolize both hexose and pentose sugars or microbial consortia consisting of substrate-selective microbes-may be advantageous. This study presents a detailed in silico analysis of bioethanol production from glucose-xylose mixtures of various compositions by batch mono-culture and co-culture fermentation of specialized microbes. Dynamic flux balance models based on available genome-scale reconstructions of the microorganisms have been used to analyze bioethanol production, and the maximization of ethanol productivity is addressed by computing optimal aerobic-anaerobic switching times. Effects of ten metabolic engineering strategies that have been suggested in the literature for ethanol overproduction, have been evaluated for their efficiency in enhancing the ethanol productivity in the context of batch mono-culture and co-culture processes.