Biosynthesis of cytochalasans. Part 5. The Incorporation of Deoxaphomin into Cytochalasin B (Phomin)

Abstract

Summuvy. Radioactive deoxaphomin (1) which was obtained by feeding [4'-8H, U-W]-Lphenylalanine to cultures of Phomu sp. (S 298) was shown to be well incorporated into cytochalasin B (phomin) (2). The results demonstratc that 1 is an immediate biogcnetic precursor of 2.

Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1

“…In a previous feeding study, the successful incorporation of the 13-membered carbocyclic deoxaphomin to yield the 14-membered macrolactone-containing cytochalasin B implied the involvement of an enzymatic Baeyer-Villiger-type oxygen insertion between the C9 bridging carbon and C23 carbonyl (Robert and Tamm, 1975). Accordingly, the 13-membered macrocyclic carbonate in cytochalasin E was proposed to be originated from a corresponding 11-membered carbocyclic cytochalasan, whereby the unusual insertion of two oxygen atoms may occur via two consecutive Baeyer-Villiger oxidations (Robert and Tamm, 1975).…”

“…In a previous feeding study, the successful incorporation of the 13-membered carbocyclic deoxaphomin to yield the 14-membered macrolactone-containing cytochalasin B implied the involvement of an enzymatic Baeyer-Villiger-type oxygen insertion between the C9 bridging carbon and C23 carbonyl (Robert and Tamm, 1975). Accordingly, the 13-membered macrocyclic carbonate in cytochalasin E was proposed to be originated from a corresponding 11-membered carbocyclic cytochalasan, whereby the unusual insertion of two oxygen atoms may occur via two consecutive Baeyer-Villiger oxidations (Robert and Tamm, 1975). In nature, such Baeyer-Villiger oxidations of ketones are known to be mediated by flavin-containing proteins collectively known as Baeyer-Villiger monooxygenases (BVMOs), which can be classified into type I, type II and type “O” with the type I BVMOs being the most commonly found (Leisch et al, 2011).…”

Chemistry and Biology of Biosynthetic Diels–Alder Reactions

“…[28] Incorporation of deoxaphomin (57) into 51 indicates that oxidation to the macrolide occurs after the putative Diels-Alder cyclization and implies there is a common biosynthetic pathway for the cytochalasans. [34] Indirect evidence for the Diels-Alder-mediated biosynthesis of the cytochalasins was obtained by feeding [35] and inhibition [36] experiments with Chaetomium subaffine, which produces chaetoglobosin A (58, Scheme 12). A feeding experiment with [1-13 C,2-2 H 3 ]acetate showed retention of the deuterium labels at C11, C8, and C14.…”

A carbonate-forming Baeyer-Villiger monooxygenase

“…Such activities were demonstrated in the classical feeding studies of deoxaphomin (ketone version of cytochalasin B) to Phoma sp. and the recovery of cytochalasin B 23 . We therefore propose that formation of the carbonate product by CcsB is the fortuitous result of the perfectly arranged functional groups near the ketone site in 7 and 11 .…”