Uncovering biosynthetic relationships between antifungal nonadrides and octadrides

J., Kate M.; 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.

doi:10.1039/d0sc04309e

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Uncovering biosynthetic relationships between antifungal nonadrides and octadrides

Kate M. J. de Mattos-Shipley, Catherine E. Spencer

, 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

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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...

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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

first_indexed	2022-10-20T11:41:32Z
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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).</funders><projectreference/><lastEdited>2022-10-20T12:42:48.9419358</lastEdited><Created>2022-10-10T17:25:00.2732449</Created><path><level id="1">Faculty of Science and Engineering</level><level id="2">School of Biosciences, Geography and Physics - Biosciences</level></path><authors><author><firstname>Kate M. 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spelling	2022-10-20T12:42:48.9419358 v2 61521 2022-10-10 Uncovering biosynthetic relationships between antifungal nonadrides and octadrides cacac6459bd7cf4a241f63661006036f 0000-0003-3067-0999 Claudio Greco Claudio Greco true false 2022-10-10 BGPS 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. Journal Article Chemical Science 11 42 11570 11578 Royal Society of Chemistry (RSC) 2041-6520 2041-6539 7 10 2020 2020-10-07 10.1039/d0sc04309e COLLEGE NANME Biosciences Geography and Physics School COLLEGE CODE BGPS Swansea University 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). 2022-10-20T12:42:48.9419358 2022-10-10T17:25:00.2732449 Faculty of Science and Engineering School of Biosciences, Geography and Physics - Biosciences Kate M. J. de Mattos-Shipley 1 Catherine E. Spencer 0000-0001-8174-0913 2 Claudio Greco 0000-0003-3067-0999 3 David M. Heard 0000-0003-3005-8222 4 Daniel E. O'Flynn 5 Trong T. Dao 0000-0003-4741-1678 6 Zhongshu Song 7 Nicholas P. Mulholland 8 Jason L. Vincent 9 Thomas J. Simpson 0000-0003-0777-1935 10 Russell J. Cox 0000-0002-1844-0157 11 Andrew M. Bailey 0000-0002-7594-3703 12 Christine L. Willis 0000-0002-3919-3642 13 61521__25518__d6ecbaf803954090958a221ad1de1a0b.pdf 61521_VoR.pdf 2022-10-20T12:41:58.0618988 Output 1574012 application/pdf Version of Record true This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. true eng http://creativecommons.org/licenses/by/3.0/
title	Uncovering biosynthetic relationships between antifungal nonadrides and octadrides
spellingShingle	Uncovering biosynthetic relationships between antifungal nonadrides and octadrides Claudio Greco
title_short	Uncovering biosynthetic relationships between antifungal nonadrides and octadrides
title_full	Uncovering biosynthetic relationships between antifungal nonadrides and octadrides
title_fullStr	Uncovering biosynthetic relationships between antifungal nonadrides and octadrides
title_full_unstemmed	Uncovering biosynthetic relationships between antifungal nonadrides and octadrides
title_sort	Uncovering biosynthetic relationships between antifungal nonadrides and octadrides
author_id_str_mv	cacac6459bd7cf4a241f63661006036f
author_id_fullname_str_mv	cacac6459bd7cf4a241f63661006036f_***_Claudio Greco
author	Claudio Greco
author2	Kate M. J. de Mattos-Shipley Catherine E. Spencer 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
format	Journal article
container_title	Chemical Science
container_volume	11
container_issue	42
container_start_page	11570
publishDate	2020
institution	Swansea University
issn	2041-6520 2041-6539
doi_str_mv	10.1039/d0sc04309e
publisher	Royal Society of Chemistry (RSC)
college_str	Faculty of Science and Engineering
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department_str	School of Biosciences, Geography and Physics - Biosciences{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Biosciences, Geography and Physics - Biosciences
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description	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.
published_date	2020-10-07T20:28:53Z
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Uncovering biosynthetic relationships between antifungal nonadrides and octadrides

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