Efficient synthesis of tyrosol from L-tyrosine via heterologous Ehrlich pathway in Escherichia coli

Abstract

For the efficient conversion of L-tyrosine (L-Tyr) to tyrosol, which is an aromatic compound widely used in the pharmaceutical and chemical industries, a novel four-enzyme cascade pathway based on the Ehrlich pathway of Saccharomyces cerevisiae was designed and reconstructed in Escherichia coli. Then, the expression levels of the relevant enzymes were coordinated using a modular approach and gene duplication after the identification of the pyruvate decarboxylase from Candida tropicalis (CtPDC) as the rate-limiting enzymatic step. In situ product removal (ISPR) strategy with XAD4 resins was explored to avoid product inhibition and further improve tyrosol yield. As a result, the titer and conversion rate of tyrosol obtained were 35.7 g·L−1 and 93.6%, respectively, in a 3-L bioreactor. Results presented here provide a potential enzymatic process for industrial production of tyrosol from cheap amino acids.