Reaction Engineering of Biocatalytic Enantioselective Reduction: A Case Study for Aliphatic Ketones

Abstract

Previously, it could be demonstrated, that the monophasic, enzymatic reduction of aliphatic 2-ketones into the corresponding (R)-2-alcohols is an adequate and viable method as carried out in a cascade of two enzyme−membrane reactors (Leuchs, S.; Na'amnieh, S. N.; Greiner, L. Green Chemistry 2013, 15, 167−176.). In the present work, the process metrics of the ketone reduction were calculated. A cost analysis revealed that the enzyme costs are negligible, but the cost for nicotinamide cofactor NADP + is dominating the overall cost of the chemical raw material followed by the ionic liquid (TEGO IL K5) used as solubiliser and the buffer. The overall cost of chemicals was €148/kg product . To assess the environmental impact of the process, the E-factor (kg waste /kg product ) 132 and the process mass intensity 133 (PMI, kg substrate /kg product ) were calculated. A process model based on initial rate experiments was elaborated and used to improve the process under cost and environmental aspects. Applying several measures to enhance the cofactor utilisation, the cost base could be reduced by 65% and the E-factor (PMI) to 17 (18).

A two-step biocatalytic cascade in micro-aqueous medium: using whole cells to obtain high concentrations of a vicinal diol

“…Recently, the highest cost contribution in an enzymatic process was attributed to NADP + even when the cofactor is recycled. 35 Additionally, the E-factor, describing the mass of waste per mass of product, of the optimised cascade is 21.3 kg waste kg product −1 (ESI Table S5 †) rendering this process very ecofriendly. [35][36][37] Concerning product work-up, laborious and waste-generating solvent extraction was omitted as the product was readily available in MTBE.…”

“…35 Additionally, the E-factor, describing the mass of waste per mass of product, of the optimised cascade is 21.3 kg waste kg product −1 (ESI Table S5 †) rendering this process very ecofriendly. [35][36][37] Concerning product work-up, laborious and waste-generating solvent extraction was omitted as the product was readily available in MTBE. Including work-up, however, the E-factor increases to 1927 kg waste kg product −1 (ESI Table S5 †), which is beyond that desirable in E-factor ranges.…”

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

“…This process underscores the development of biocatalysis to enable efficient, economical, and environmentally benign processes for the manufacture of pharmaceuticals. 2 However, despite a huge interest in transaminase catalysed reactions, 2,[9][10][11][12][13] they are often challenging to implement on an industrial scale due to frequent thermodynamic and kinetic challenges. 10 To shift the reaction equilibrium towards the wanted products, 9,11,12 transaminases can be coupled with other enzymes forming cascade reaction systems.…”

Primjena matematičkog modeliranja u razvoju enzimskih kaskadnih reakcija

“…Leuchs i sur. 12 demonstrirali su kako se matematičko modeliranje u biokatalizi može primijeniti ne samo u optimizaciji već i u procjeni ekonomičnosti procesa te njegova utjecaja na okoliš. Kako bi bile konkurentne kemijskoj sintezi, kaskadne reakcije trebaju biti učinkovite, robusne i samoodržavajuće, te bi bilo idealno da se provode in vitro u jednom reaktoru.…”