Uncovering biosynthetic relationships between antifungal nonadrides and octadrides. Issue 42 (7th October 2020)

• Record Type: Journal Article
• Authors: de Mattos-Shipley, Kate M. J.; Spencer, Catherine E.; Greco, Claudio; Heard, David M.; O'Flynn, Daniel E.; Dao, Trong T.; Song, Zhongshu; Mulholland, Nicholas P.; Vincent, Jason L.; Simpson, Thomas J.; Cox, Russell J.; Bailey, Andrew M.; Willis, Christine L.
• Is Part Of: Chemical science. Volume 11:Issue 42(2020)
• Page Start: 11570
• Page End: 11578
• Publication Date: 2020-10-07
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0sc04309e
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Deoxyscytalidin is a common biosynthetic intermediate to the nonadride scytalidin in the fungus Scytalidium album and in Diffractella curvata gives the octadride zopfiellin. Abstract : Maleidrides are a class of bioactive secondary metabolites unique to filamentous fungi, which contain one or more maleic anhydrides fused to a 7-, 8- or 9- membered carbocycle (named heptadrides, octadrides and nonadrides respectively). Herein structural and biosynthetic studies on the antifungal octadride, zopfiellin, and nonadrides scytalidin, deoxyscytalidin and castaneiolide are described. A combination of genome sequencing, bioinformatic analyses, gene disruptions, biotransformations, isotopic feeding studies, NMR and X-ray crystallography revealed that they share a common biosynthetic pathway, diverging only after the nonadride deoxyscytalidin. 5-Hydroxylation of deoxyscytalidin occurs prior to ring contraction in the zopfiellin pathway of Diffractella curvata . In Scytalidium album, 6-hydroxylation – confirmed as being catalysed by the α-ketoglutarate dependent oxidoreductase ScyL2 – converts deoxyscytalidin to scytalidin, in the final step in the scytalidin pathway. Feeding scytalidin to a zopfiellin PKS knockout strain led to the production of the nonadride castaneiolide and two novel ring-open maleidrides.