Optimized Enzyme Production for the Escherichia coli Whole-Cell Biocatalytic Synthesis of Codeine from Thebaine

Abstract

Codeine, the most widely used medicinal opiate in the world, can be produced from thebaine by using an environmentally friendly biocatalytic process using purified enzymes or microbial cells. However, this biotransformation is either inefficient or not systematically characterized for industrial use, as microbial fermentation and enzyme expression have not been optimized, and the production of the undesirable side product neopine reduces yields. In this study, the expression of the required enzymes in a reengineeredEscherichia coli system was optimized using a two-step design of experiments approach. Higher yields of biomass and enzyme expression were achieved in a defined minimal medium usi..