BASF Lectureship in Chemical Sciences: Studies of the Assembly of the Thioheptose Core of Albomycins
Seminar | November 12 | 11 a.m.-12 p.m. | 120 Latimer Hall
Sulfur is an essential element for life and is found in all living systems. Yet, how the sulfur is incorporated in many sulfur-containing secondary metabolites remains poorly understood. Albomycin δ2 is an unusual naturally occurring nucleoside that possesses a sulfur-containing furanose, which is essential for its potent antibiotic activity against clinically important pathogens. The structure of albomycin is characterized by a thioheptose core with atypical stereochemistry including a D-xylofuranose ring modified with a D-amino acid moiety. During the biosynthesis of albomycin δ2, a pyridoxal 5′-phosphate (PLP)-dependent transaldolase catalyzes a threo-selective aldol-type reaction to generate the thioheptose core with a D-ribofuranose ring modified with an L-amino acid moiety. The D-amino acid configuration is then introduced by another PLP-dependent epimerase. Furthermore, the D-ribo to D-xylo conversion of the thiofuranose ring is mediated by a radical S-adenosyl-L-methionine (SAM) enzyme. Recently, we have identified another radical SAM enzyme that catalyzes construction of the thiofuranose ring via sulfur incorporation into cytidine 5′-diphosphate. These results will be presented in the lecture.