Employing racemic precursors in directed biosynthesis of 6-dEB analogs

Substitution of racemic diketide thioesters for optically pure compounds in precursor-fed fermentations was investigated. These substrates were shown to be as effective as optically pure materials in diketide-fed fermentation processes for producing analogs of 6-deoxyerythronolide B. However, since half of the racemic mixture is not utilizable for polyketide biosynthesis, higher total levels of diketide are required. Toxicity to cells was evident at high diketide concentrations. In fermenters, exhaust gas analysis was used to indicate the optimal time for diketide addition. While both enantiomers were shown to disappear from cultures at similar rates, the presence of unincorporated enantiomer had minimal effect on polyketide production within a range of feed concentrations. Use of racemic diketide thioesters was successful and dramatically reduced the cost of the fermentation process. (C) 2002 Society of Chemical Industry.