ABSTRACT

This chapter discusses the reader to the new and emerging field of synthetic multi-step enzymatic cascades. The use of single-step biocatalytic reactions in chemical syntheses, using protein-engineered enzymes to transform unnatural substrates to important pharmaceutical intermediates, is an established technology for commercial production. The use of one-pot multi-step cascades in chemical syntheses has clear advantages in terms of process intensification compared to multiple single step reactions. Enzyme immobilisation and fusion protein generation strategies were both adopted in a one-pot four-enzyme system for the synthesis of dihydroxyacetone phosphate from glycerol. N. J. Turner and co-workers developed a sequential one-pot, three step, chemoenzymatic synthesis to produce a range of N-protected non-natural (d)-biarylalanine derivatives starting from 4-bromophenylpyruvic acid. Mutual inactivation by chemo- and biocatalysts and reaction condition incompatibilities are the major challenges for chemoenzymatic cascades. The resulting processes will minimise the isolation of intermediates and decrease unit operations, which has a direct impact on waste reduction and lowering costs.