Glucose-1-phosphate thymidylyltransferase promotes the production of 3-O-α-mycarosylerythronolide B in Streptomyces coelicolor.

Aims: The main objective of this study was to produce erythronolide B (EB) and 3-O-α-mycarosylerythronolide B (MEB) in Streptomyces coelicolor and enhance the MEB production by expressing the glucose-1-phosphate thymidylyltransferase (RfbA).

Methods and results: We expressed eryF and eryB genes (eryBII, eryBIII, eryBIV, eryBV, eryBVI and eryBVII) to produce EB and MEB. The expression was confirmed by quantitative real-time PCR. Furthermore, the MEB's production was improved by more than 100-fold by expressing an enzyme, RfbA, which is absent from the erythromycin gene cluster, to promote the biosynthesis of TDP-L-mycarose. We discuss the feasibility of alternative Streptomyces species for erythromycin production based on the presence or absence of RfbA.

Conclusions: The RbfA enzyme from Saccharopolyspora erythraea was expressed in S. coelicolor M1152 along with the MEB biosynthesis pathway, resulting in a large increase in MEB production (>100-fold).