Our group is interested in structure/function relationship of enzymes involved in anthracycline biosynthetic gene clusters. Our group focuses on the expression, purification and characterization of enzymes involved in anthracycline biosynthesis. Through our collaborations with Streptomyces Research group from our department and Division of Molecular Structural Biology at Karolinska Institute the structure/function relationship of anthracycline biosynthetic enzymes.
My PhD will focus on two topics. Firstly, structural and functional studies of two enzymes from the gene cluster of Streptomyces nogalater, SnoaM and SnoaB. They perform consecutive reactions in the anthracyclin nogalamycin. SnoaM, a putative polyketide cyclase, is thought to be involved in the cyclation of two rings within the four-ringed aglycon structure. SnoaB,a monooxygenase, is involved adding double bonded oxygen to the aglycon structure. By studying the structure and function of both enzymes, many homologous enzymes involved in similar anthracyclin clusters will be better understood.
Secondly, by protein engineering both enzymes RdmB and DnrK the relationship between structure and function will be investigated further. Both enzyme structures are already known. This study should provide further insight into the evolutionary mechanism of biosynthetic gene clusters.