Engineering a Biometallic Whole Cell Catalyst for Enantioselective Deracemization Reactions

Abstract

The ability of microbial cells to synthesize highly reactive nanoscale functional materials provides the basis for a novel synthetic biology tool for developing the next generation of multifunctional industrial biocatalysts. Here, we demonstrate that aerobic cultures of Escherichia coli, genetically engineered to overproduce a recombinant monoamine oxidase possessing high enantioselectivity against chiral amines, can be augmented with nanoscale Pd(0) precipitated via bioreduction reactions. The result is a novel biometallic catalyst for the deracemization of racemic amines. This deracemization process is normally achieved by discrete sequential oxidation/reduction steps using a separate enantiomer-specific biocatalyst and metal catalyst, respectively. Here, use of E. coli cultures carrying the cloned monoamine oxidase gene and nanoscale bioreduced Pd(0) particles was used successfully for the conversion of racemic 1-methyltetrahydroisoquinoline (MTQ) to (<i>R</i>)-MTQ, via the intermediate 1-methyl-3,4-dihydroisoquinoline, with an enantiomeric excess of up to 96%. There was no loss of catalyst activity following the five rounds of oxidation and reduction, and importantly, there was minimal loss of palladium into the reaction supernatant. This first demonstration of a whole cell biometallic catalyst mixture for “single-pot”, multistep reactions opens up the way for a wide range of integrated processes, offering a scalable and highly flexible platform technology