Combinatorial approach to the selection of active microorganisms in biotransformation: Application to sinomenine

Abstract

► Screening method was elaborated involving series of 12 microorganisms. ► Combinatorial mixtures have reduced the number of tests to a third compared to the traditional approach. ► One microorganism acting on each substrate was selected, each one producing two metabolites. There is an obvious increasing interest to take advantage of microorganisms as natural reagents in organic synthesis. That requires to efficiently select the microorganism able to transform the molecule of interest. We disclose a combinatorial approach, which significantly reduces the number of assays. This new strategy in screening active microorganisms is based on incubation of mixtures of biomasses, in place of one-at-a-time screening strategies. By applying our method to sinomenine derivatives in a hemisynthesis context, we quickly identified two microorganisms in 8 and 10 assays among twenty-four microorganisms, for their abilities to metabolize this morphinane alkaloid into N -deprotected, N -oxide and dioxygenated metabolites.