Identification and characterization of the biosynthetic gene cluster of divergolides from Streptomyces sp. W112

Strategies to diversify natural products for drug discovery

“…Laboratory-based chemical investigations of endophytes for obtaining diverse and bioactive secondary metabolites have been covered in several reviews. 24,51,[66][67][68] In such studies, endophytes produce a wealth of specialized metabolites, mainly including structurally complex polyketides, [69][70][71][72][73] linear or cyclic nonribosomal peptides, 74,75 polycyclic terpenes 76,77 , rearranged steroids, 78 and hybrid peptide/polyketide or terpene/polyketide natural products [79][80][81] .…”

“…The antifungal drug caspofungin acetate (CANCIDAS R , 70) (Fig. 21) is a semisynthetic derivative of pneumocandins A 0 (71) and B 0 (72), which are natural lipohexapeptides of the echinocandin family and inhibit the synthesis of 1,3--D-glucan in fungal cell walls. 214,215 In order to obtain more analogues for antifungal drug development, Bills and co-workers carried out the insertional inactivation of three pathway genes (GLP450-1, GLP450-2, or GLOXY1) in the pneumocandin biosynthetic gene cluster, identifying 13 different pneumocandin analogues (73-85) (Fig.…”

Total Synthesis of Divergolides E and H

“…Hertweck and co‐workers showed that, despite impressive structural heterogeneity resulting from differences in oxidation state and hydration levels, these compounds are derived from the same polyketide synthase system . Subsequent studies based on genomic analyses provided greater insights into the biosyntheses of these structures . Structurally disparate members of this family (Figure ) include the bridged bicyclic acetal divergolide E ( 1 ), the naphthoquinone divergolide I ( 2 ), and the alkylidene chromene divergolide B ( 3 ).…”

Total Synthesis of Divergolides E and H

“…[1] Hertweck and co-workers showed that, despite impressive structural heterogeneity resulting from differences in oxidation state and hydration levels,these compounds are derived from the same polyketide synthase system. [1c, 2, 3] Structurally disparate members of this family (Figure 1) include the bridged bicyclic acetal divergolide E( 1), the naphthoquinone divergolide I ( 2), and the alkylidene chromene divergolide B( 3). [1c, 2, 3] Structurally disparate members of this family (Figure 1) include the bridged bicyclic acetal divergolide E( 1), the naphthoquinone divergolide I ( 2), and the alkylidene chromene divergolide B( 3).…”

“…[1a] Subsequent studies based on genomic analyses provided greater insights into the biosyntheses of these structures. [1c, 2, 3] Structurally disparate members of this family (Figure 1) include the bridged bicyclic acetal divergolide E( 1), the naphthoquinone divergolide I ( 2), and the alkylidene chromene divergolide B( 3). These compounds have been reported to show moderate antibiotic activity against an umber of strains,i ncluding some that show drug resistance,though these studies are limited to zone inhibition assays.T hese structures have been the subject of several synthetic studies [4] and the total synthesis of 2,t he only member of the family to be synthesized, was recently reported by Tr auner and co-workers.…”