Division of labour: The rapid enzyme inactivation in the electroenzymatic synthesis of chiral alcohols has been the main obstacle for synthetic applications during the last two decades. The reasons for this inactivation have now been elucidated. The development of a water-soluble polymeric mediator and the spatial separation of enzyme and mediator led to the first stable process and significantly improved catalyst utilisations (see picture).
Electroenzymatic synthesis often suffers from electrochemical reaction steps which proceed slower than the coupled enzyme reaction. For indirect electrochemical cofactor regeneration, we here report two new mediators with superior properties compared to the established rhodium complex (2,2'-bipyridyl)(pentamethylcyclopentadienyl)rhodium [Cp*Rh(2,2'-bipyridine)]. After constructing a robotic system for fast and reliable cyclic voltammetry measurements, we screened twelve rhodium complexes with substituted 2,2'-bipyridine ligands for their reduction potentials and catalytic activity towards the reduction of NADP. Promising complexes were investigated in more detail by cyclic voltammetry and under batch electrolysis conditions. The new complexes Cp*Rh(5,5'-methyl-2,2'-bipyridine) and Cp*Rh(4,4'-methoxy-2,2'-bipyridine) reduced NADP to NADPH three times faster than the established mediator, resulting in volumetric productivities of up to 136 mmol L À1 d À1 and turnover frequencies of up to 113 h
À1. This increased reaction rate of these new mediators makes indirect electrochemical approach significantly more competitive to other methods of cofactor regeneration.Abbreviations: ADH = alcohol dehydrogenase; Ag j AgCl = silver j silver chloride reference electrode; bpy = 2,2'-bipyridine; ci = current increase; Cp* = pentamethylcyclopentadienyl; CV = cyclic voltammetry; Ep = peak potential; equiv = equivalent; NADP/ NADPH = nicotinamide adenine dinucleotide phosphate oxidised/reduced form.
Benzaldehyde lyase (BAL; E.C. 4.1.2.38) from Pseudomonas fluorescens Biovar I catalyzes the reversible formation of benzoins from aromatic aldehydes, and, moreover, the coupling of aromatic with aliphatic aldehydes yielding derivatives of (R)-2-hydroxy-1-phenyl- propan-1-one (R)-HPPs), which are important chiral building blocks. In this paper, we report on the development of a reactor system that allows the selective production of substituted (R)-HPP-derivatives. The reaction systems yielding (R)-1-(3-chloro-phenyl)-2-hydroxy- propan-1-one, (R)-2-hydroxy-3-methoxy-1-(4-methoxy-phenyl)-propan-1-one, and (R)-2-hydroxy-3,3-dimethoxy-1-phenyl-propan-1-one were investigated. A kinetic model optimized by batch experiments was developed, for the description of both batch and continuously operated reactors. This model was used to describe the HPP production in a continuously operated enzyme membrane reactor. The reactor type used combines the advantages of high conversion and excellent selectivity with high space-time yields and total turnover numbers of up to ttn=43,000. Products were obtained in high yield on a gram scale.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.