Uncovering Biosynthetic Relationships Between Antifungal Nonadrides and Octadrides
| Autor: | Kate M. J. de Mattos-Shipley, Christine L. Willis, Andy M. Bailey, Trong Tuan Dao, Zhongshu Song, David M. Heard, Nicholas Phillip Mulholland, Daniel E. O’Flynn, Claudio Greco, Thomas J. Simpson, Catherine E Spencer, Russell J. Cox, Jason Leigh Vincent |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Antifungal
Dewey Decimal Classification::500 | Naturwissenschaften::540 | Chemie Filamentous fungi medicine.drug_class Knockout strains 010402 general chemistry Biosynthesis Genome sequencing 01 natural sciences DNA sequencing BCS and TECS CDTs Oxidoreductase Bioinformatic analysis medicine Metabolites Ring contraction Gene Scytalidium album X-ray crystallography chemistry.chemical_classification Zopfiellin biology 010405 organic chemistry Secondary metabolites Bristol BioDesign Institute General Chemistry biology.organism_classification Gene disruptions 0104 chemical sciences Chemistry Biosynthetic pathway Biochemistry chemistry ddc:540 Diffractella |
| Zdroj: | De Mattos-Shipley, K M J, Spencer, C E, Greco, C, Heard, D M, O'Flynn, D E, Dao, T T, Song, Z, Mullholland, N P, Vincent, J L, Simpson, T J, Cox, R J, Bailey, A M & Willis, C L 2020, ' Uncovering Biosynthetic Relationships Between Antifungal Nonadrides and Octadrides ', Chemical Science, vol. 11, pp. 11570-11578 . https://doi.org/10.1039/D0SC04309E Chemical Science 11 (2020), Nr. 42 Chemical Science |
| Popis: | 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. Deoxyscytalidin is a common biosynthetic intermediate to the nonadride scytalidin in the fungus Scytalidium album and in Diffractella curvata gives the octadride zopfiellin. |
| Databáze: | OpenAIRE |
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