An economically and environmentally acceptable synthesis of chiral drug intermediate l-pipecolic acid from biomass-derived lysine via artificially engineered microbes

Abstract

Abstract Deficiency in petroleum resources and increasing environmental concerns have pushed a bio-based economy to be built, employing a highly reproducible, metal contaminant free, sustainable and green biomanufacturing method. Here, a chiral drug intermediate l-pipecolic acid has been synthesized from biomass-derived lysine. This artificial bioconversion system involves the coexpression of four functional genes, which encode l-lysine α-oxidase from Scomber japonicus, glucose dehydrogenase from Bacillus subtilis, Δ1-piperideine-2-carboxylase reductase from Pseudomonas putida, and lysine permease from Escherichia coli. Besides, a lysine degradation enzyme has been knocked out to strengthen the process in this microbe. The overexpression of LysP improved the l-pipecolic acid titer about 1.6-folds compared to the control. This engineered microbial factory showed the highest l-pipecolic acid production of 46.7 g/L reported to date and a higher productivity of 2.41 g/L h and a yield of 0.89 g/g. This biotechnological l-pipecolic acid production is a simple, economic, and green technology to replace the presently used chemical synthesis.