Sporolide B Synthesis « Naturalproductman’s Blog
Based on the postulated biosynthesis of the sporolides (I + II → 1b), the first approach (Path a, ) was considered risky, despite the rather conventional steps required for its implementation, due to the expected lability of some of the obligatory intermediates.
Total Synthesis of Sporolide B and 9- epi -Sporolide B | …
Sporolides A and B (1) are polycyclic macrolides from the marine actinomycete Salinispora tropica with a previously undescribed molecular architecture. Sequencing of the 5 183 331 bp S. tropica CNB-440 genome has shed light into sporolide biosynthesis, which is highlighted by an enediyne po ketide synthase and an unexpected tyrosine degradation pathway. In this paper, we describe the in vitro characterization of the biosynthetic gene spoT1, which is involved in the initial biochemical reaction to the highly functionalized cyclohexenone unit of 1.
These three highly related EHs present an outstanding opportunity to probe the basis for regioselectivity in enediyne biosynthesis and bioinformatically assign the stereochemical configuration of new enediynes. Herein we identify a rare EH tyrosine-to-tryptophan mutation in SgcF that influences regioselectivity. Genome mining for this mutation in enediyne biosynthesis-associated EHs identified two additional enzymes (SpoF from Salinospora tropica CNB-440 and SgrF from Streptomyces griseus IFO 13350) that were biochemically confirmed as inverting EHs. The predictive utility of this model was expanded by the observed phylogenetic separation of enediyne biosynthesis-associated EHs into inverting and retaining groups. In addition, the location of spoF within the gene cluster encoding the biosynthesis of the (R)-diol-containing sporolides suggests that this sequence-based model may be used to predict the stereochemical configuration of proposed 9-membered enediynes identified from genome sequencing projects.