Application of Chemical Engineering Methodology in Process Development: A Case Study of MenD-catalyzed Synthesis of 6-Cyano-4-oxohexanoic Acid

Abstract

To speed up evaluation, development and upscaling of new processes, the use of engineering methodology can have a great impact. Here we show the application of an engineering approach to find the reaction conditions allowing the best process metrics. An experimentally validated mathematical model for the MenD-catalyzed synthesis of a commercially unavailable product, 6-cyano-4-oxohexanoic acid, with a potential industrial use as a building block, was used for process optimization. Using the optimized conditions, 62.4 g dm-3 of product, volume productivity of 87.1 g dm-3 d-1 , product yield of 96 %, and biocatalyst productivity of 25.8 kg P kg-1 MenD can be achieved. Based on the optimized production procedure, economic analysis was performed to determine minimal product price required for project to be profitable in 8 years economic lifetime. In addition, Monte Carlo analysis (MCA) was used to assess the influence of uncertainties in estimation of input variables on overall economic performance.

Biocatalysis in the Age of the Green Revolution

“…To uključuje primjenu modeliranja, 72,73 metoda za optimiranje procesa, [74][75][76] a također i primjenu metoda za ekonomsku procjenu procesa još u ranom stadiju razvoja. [77][78][79] Metodologija koja uključuje modeliranje može se primjenjivati u svrhu definiranja prostora za pronalazak optimalnog rješenja, 80,81 može smanjiti troškove i skratiti vrijeme razvoja s obzirom na to da simulacije mogu povećati razumijevanje procesa, 73,82,83 a može imati i povoljan utjecaj na kvalitetu produkta. 84 Farmaceutska industrija ulaže više novaca u istraživanje i razvoj procesa koji ne budu odobreni nego u uspješne procese; 85 razvoj lijeka koji uspije doći do faze kliničkih istraživanja u prosjeku traje 10 -15 godina i pri tome se potroši 1 -2 milijarde dolara, a unatoč tome 90 % ih ne bude odobreno za prodaju, 86,87 što ilustrira važnost potrebe smanjenja troškova i vremena razvoja industrijskih procesa.…”