Ardao, InésInésArdaoZeng, An-PingAn-PingZeng2020-08-072020-08-072012-10-11Chemical Engineering Science (87): 183-193 (2013)http://hdl.handle.net/11420/6988Multi-enzymatic processes are becoming increasingly attractive for the production of chemicals and pharmaceuticals at an industrial level due to a drastic reduction on the down-stream steps that leads to a better exploitation of resources. One-pot processes (all the enzymes placed in the same reactor) are the most commonly used approach although they present a number of limitations. In this work we explore the use of modular processes (enzymes distributed in different reactors) as an alternative to overcome the limitations of one-pot processes. An in silico evaluation of different process alternatives was performed, taking as an example a multi-enzymatic system for high-yield production of hydrogen from biomass catalyzed by a synthetic metabolic pathway composed of 13 enzymes. A modular process where an hyperthermophilic hydrogenase is kept at higher temperature than the rest of the enzymes lead to a 2-fold increase in productivity, whereas a separate reactor that consumes an inhibitor of other enzymes lead to an 8-fold increase in productivity, compared to the one-pot operation. A multi-objective optimization of the one-pot process for the maximization of productivity and yield was also performed using a genetic algorithm. Productivities of up to 355mmol/L/h was expected to be achieved without compromising the high yield of the process (11.3mol of H2 produced per mol substrate) under the conditions studied. © 2012 Elsevier Ltd.en0009-25092012183193Elsevier ScienceBiochemical engineeringMathematical modelingMulti-enzymatic systemMulti-objective optimizationReaction engineeringSimulationChemieBiowissenschaften, BiologieTechnische ChemieJournal Article10.1016/j.ces.2012.10.005Other