Cascade enzymatic synthesis of l-homoserine – mathematical modelling as a tool for process optimisation and design

Abstract

L-Homoserine is an important compound and a building block in the chemical and pharmaceutical industry. The one-pot cascade synthesis of L-homoserine with substrate recycling catalysed by an aldolase and a transaminase was investigated in detail, with special interest in the reaction's kinetics and process development. Complex relationships between the process variables were discovered and kinetic and reactor models were developed. In addition, new chemical insights were developed through this model-driven process development, and for the first time, a kinetic model was proposed to describe YfaU-catalysed reactions. The modelling was crucial for a better understanding of the reaction system, as well as for process optimisation. Finding a suitable strategy for process improvement by manipulating the reaction conditions, as well as developing a process design, was imperative to obtain the process metrics necessary for scale-up. Using the optimized reaction conditions in the fed-batch reactor with a continuous formaldehyde supply, and with subsequent addition of pyruvate and L-alanine, 80.1 g L⁻¹L-homoserine was obtained with a volume productivity of 3.2 g L⁻¹ h⁻¹ after 25 h. These results present a 100% increase in product concentration and an approximately 18% increase in volume productivity in comparison with previously published work. This work shows the benefit of the synergistic approach of bio(chemical) knowledge and process model development working hand-in-hand which is crucial for greater breakthroughs of biocatalysis in the chemical industry.