Modelling Enzymatic Reduction of 2-keto-D-glucose by Suspended Aldose Reductase

Genetically engineered enzymes of modified structure are proved very effective biocatalysts for many biosyntheses of industrial interest, which tend more and more to replace some of the classical fine chemical synthesis processes. Engineered enzymatic reactions, displaying a high selectivity and specificity, are sustainable bioengineering routes to obtain a wide range of biochemical products in food, pharmaceutical, detergent, textile industry, bio-renewable energy industries, or present challenging applications in medicine.1,2 Biocatalytic processes produce fewer by-products, consume less energy, and generate less environmental pollution, require smaller catalyst concentrations and moderate reaction conditions. However, the crucial aspect in any realistic engineering analysis for process design, operation, control, and optimization relies on the knowledge of an adequate and sufficiently reliable mathematical model. Such a model, preferably based on the process mechanism and developed at various detailing levels (enzyme, reaction, reactor, process, separately identified and linked using specific methodologies), has to ensure interpretable and reliable predictions of the process behaviour under varied operating conditions.2–4 In particular, special attention was paid over the decades to aldose reductase (EC 1.1.1.21, aldehyde reductase), being justified by its medical applications: involvement of ALR in the glucose metabolism (glucose conversion to sorbitol, galactose reduction to galactitol), development of diabetic cataract (leading to eye and nerve damage due to sorbitol overproduction),5 of the myocardial ischemic injury,6 and other putative physiological processes related to steroid and catecholamine metabolism.7 As a member of the aldo-keto reductase superfamily,7 the ALR catalyzes the NADPH-dependent unspecific reduction of a wide variety of carbonyl-containing aliphatic and aromatic compounds to their corresponding alcohols, and especially of aldoses, and corticosteroids (although the enzyme can also utilize the cheaper NADH instead).8,9 For such reasons, ALR has high potential for industrial applications, e.g. for the production of Modelling Enzymatic Reduction of 2-keto-D-glucose by Suspended Aldose Reductase