Discovery of pentaene polyols by the activation of an enediyne gene cluster: biosynthetic implications for 9-membered enediyne core structures

Abstract

The identification and characterization of enediyne polyketide synthases (PKSE) revealed that PKSE-bound polyene is a common intermediate, while its subsequent tailoring steps to enediyne cores remains obscure. Herein, we report...

Jejucarbosides B–E, Chlorinated Cycloaromatized Enediynes, from a Marine Streptomyces sp.

“…Chemical analysis of the strain Streptomyces sp. JJC13 identified a series of compounds, along with the previously-reported jejucarboside A [15]. The UV spectra of the compounds were virtually identical to that of jejucarboside A, and their mass spectrometric data clearly displayed the characteristic mono-chlorinated pattern, [M+H] + :[M+2+H] + = 3:1 (Figure S1).…”

“…Considering that 9-membered enediynes are extremely rare, i.e., only five intact uncyclized 9-membered enediynes (neocarzinostatin [1], C-1027 [7], kedaricidin [8], maduropeptin [9], and N1999A2 [10]) and four cycloaromatized 9-membered enediynes (sporolide [11], cyanosporaside [12], fijiolide [13], and amycolamycin [14]) have been reported over the approximately 40 years since neocarzinostatin was discovered in 1985. Therefore, the efficient selection of strains which can express 9-membered enediyne biosynthetic gene clusters [15,16], and thus produce enediyne compounds, is required rather than relying on conventional random search strategies.…”

“…(sporolide [11], cyanosporaside [12], fijiolide [13], and amycolamycin [14]) have been reported over the approximately 40 years since neocarzinostatin was discovered in 1985. Therefore, the efficient selection of strains which can express 9-membered enediyne biosynthetic gene clusters [15,16], and thus produce enediyne compounds, is required rather than relying on conventional random search strategies.…”

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“…The activation of a putative Wuliangshan ( wls ) enediyne biosynthetic gene cluster in Streptomyces species CB02130 has resulted in the isolation of three novel pentaene polyols including 26 and two cinnamic acids. 24 The authors speculate that the discovery of these pentaene polyols and the insight generated from their biological studies of enediyne polyketide synthases allows greater understanding of how nature forms 9-membered enediyne chromophores. A combination of synthesised polyketide analogues, intact protein mass spectrometry and site-directed mutagenesis has resulted in characterisation of the catalytic function and mechanism of the dehydratase domain of the gladiolin 27 polyketide synthase.…”