Drug Metabolite Screening and Synthesis

We are experienced with using our broad and unique collection of fungi (1,500, with 300 yeasts) and bacteria (500) strains, as well as human wild-type and mutant CYPs (400) and bacterial CYP102A1 (BM3) mutants (350), expressed in E. coli or S. pombe strains, especially for oxidative drug metabolite synthesis. In addition, our comprehensive collection of Streptomyces bacteria allows for the biocatalytic synthesis of glucuronides in support of your drug discovery project.

Microbial biotransformations often allow for the synthesis of drug metabolites in the most straightforward manner by late-stage derivatization, avoiding a potentially lengthy de novo synthesis.

As a first step of the synthesis, we offer metabolite screening with a TOP panel of wild-type strains and a TOP panel of CYP variants for identification of metabolite-producing strains, using LC–MS analysis. These 2 TOP panels combine a selection of the historically most successful strains. The TOP wild-type strain panel consists of 55 fungi and bacteria strains, while the TOP CYP panel contains 119 human wild-type CYP3A4, 2C19, 2C8, 2C9, 1A2, or 2D6 enzymes and bacterial CYP102A1 (BM3) mutants.

Optionally, we can expand to a screening of chemical oxidation and glucuronidation methods and a wider range of our in-house-strain collection.

As a second step, we proceed with microbial metabolite processing, including scale-up to a 10-L fermenter, work-up, purification, and structure elucidation. Optionally, we offer metabolite synthesis by chemical oxidation or glucuronidation or de novo synthesis.

As a third step, microbial metabolite scale-up is conducted in up to 100-L fermenters to produce your drug metabolites on a milligrams to grams scale.