In this work, the role of rapH and rapG regulatory genes in the biosynthesis of rapamycin, a natural product of industrial importance, produced by S. hygroscopicus was studied. Overexpression of either gene resulted in a increase in rapamycin biosynthesis, confirming their positive regulatory role, while deletion of both of these genes resulted in a complete loss of antibiotic production. This paper therefore provided an initial understanding of two elements in the regulatory pathways, with the aim of exploiting this information to enhance the fermentation yields of rapamycin.
COBISS.SI-ID: 3310200
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
In this article we show the results of research on the regulatory genes located in gene clusters for biosynthesis of three tetracycline antibiotics. We have identified regulatory genes that regulate the biosynthesis of two industrially important tetracyclines, chlortetracycline and oxytetracycline and new tetracycline chelocardin. With use of metabolic engineering methods some strains have been genetically manipulated and so obtained results allow us to have a deeper understanding of these regulatory elements and their effect on the final yield.
COBISS.SI-ID: 3580280
In this article we report the identification of a previously unidentified region of the FK506 gene cluster from S. tsukubaensis NRRL 18488 containing genes encoding provision of unusual building blocks for FK506 biosynthesis. Among others, we identified a group of genes encoding biosynthesis of the extender unit which provides the allyl group at C21 of FK506, a secondary metabolite with a potent immunosuppressant, currently registered for use after organ transplantation. Interestingly, we have identified a small independent diketide synthase system involved in the biosynthesis of allylgroup.
COBISS.SI-ID: 3754104