Journal article 437 views 30 downloads
Uncovering biosynthetic relationships between antifungal nonadrides and octadrides
,
Claudio Greco ,
David M. Heard ,
Daniel E. O'Flynn,
Trong T. Dao ,
Zhongshu Song,
Nicholas P. Mulholland,
Jason L. Vincent,
Thomas J. Simpson ,
Russell J. Cox ,
Andrew M. Bailey ,
Christine L. Willis
Chemical Science, Volume: 11, Issue: 42, Pages: 11570 - 11578
Swansea University Author:
Claudio Greco
-
PDF | Version of Record
This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Download (1.5MB)
DOI (Published version): 10.1039/d0sc04309e
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 oc...
| Published in: | Chemical Science |
|---|---|
| ISSN: | 2041-6520 2041-6539 |
| Published: |
Royal Society of Chemistry (RSC)
2020
|
| Online Access: |
Check full text
|
| URI: | https://cronfa.swan.ac.uk/Record/cronfa61521 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| 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. |
|---|---|
| College: |
Faculty of Science and Engineering |
| Funders: |
We thank BBSRC (BB/K002341/1) and Syngenta for funding
(KMJdMS, CG and ZS) and a PhD studentship BB/P504804/1
(CS). We are also grateful to MRC (MR/N029909/1) (funding
for TTD) and EPSRC (EP/L015366/1), Bristol Chemical Synthesis
Centre for Doctoral Training, which provided PhD studentships
(DMH and DOF). We are also very grateful to BBSRC and EPSRC
for funding instrumentation via the Bristol Centre for Synthetic
Biology (BB/L01386X/1). |
| Issue: |
42 |
| Start Page: |
11570 |
| End Page: |
11578 |