Microbial Engineering for Production of N-Functionalized Amino Acids and Amines

Abstract

N-functionalized amines play important roles in nature and occur, for example, in the antibiotic vancomycin, the immunosuppressant cyclosporine, the cytostatic actinomycin, the siderophore aerobactin, the cyanogenic glucoside linamarin, and the polyamine spermidine. In the pharmaceutical and fine-chemical industries N-functionalized amines are used as building blocks for the preparation of bioactive molecules. Processes based on fermentation and on enzyme catalysis have been developed to provide sustainable manufacturing routes to N-alkylated, N-hydroxylated, N-acylated, or other N-functionalized amines including polyamines. Metabolic engineering for provision of precursor metabolites is combined with heterologous N-functionalizing enzymes such as imine or ketimine reductases, opine or amino acid dehydrogenases, N-hydroxylases, N-acyltransferase, or polyamine synthetases. Recent progress and applications of fermentative processes using metabolically engineered bacteria and yeasts along with the employed enzymes are reviewed and the perspectives on developing new fermentative processes based on insight from enzyme catalysis are discussed.

Keywords: N-functionalization; bioactives; fermentation; metabolic engineering; natural products.