We have studied specificity of epothilone acyltransferases (AT), which determine the choice of extender units during polyketide biosynthesis, thus shaping the final structure of this medically important anticancer drug. We have demonstrated that by using site-directed mutagenesis, it is possible to alter specificity of AT domain. In this experiment AT domain from FKBP12 immunophylin, such as FK506 and rapamycin were used as well. The knowledge generated in the epothilone system will lead our further efforts for PKS engineering of polyketide structures such as FK506.
COBISS.SI-ID: 3401080
The expression of bacterial polyketide synthase gene clusters is often controlled by a number of different families of regulatory proteins, such as regulatory proteins from FK506. In this article, we have undertaken a comparative bioinformatic analysis of the regulatory genes present in the oxytetracycline and chlortetracycline gene clusters of Streptomyces rimosus and S. aureofaciens. We have identified a new LAL(luxR)-family regulatory gene, otcG. By applying gene disruption and over-expression experiments we have demonstrated a positive role of otcG.
COBISS.SI-ID: 3608696