Self-Protection against the Sphingolipid Biosynthesis Inhibitor Fumonisin B<sub>1</sub> Is Conferred by a <italic toggle="yes">FUM</italic> Cluster-Encoded Ceramide Synthase

ABSTRACT Fumonisin (FB) mycotoxins produced by species of the genus Fusarium detrimentally affect human and animal health upon consumption, due to the inhibition of ceramide synthase. In the present work, we set out to identify mechanisms of self-protection employed by the FB1 producer Fusarium vert...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Slavica Janevska, Iuliia Ferling, Katarina Jojić, Julia Rautschek, Sandra Hoefgen, Robert H. Proctor, Falk Hillmann, Vito Valiante
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Fusarium fumonisin B1 ceramide synthase ABC transporter metabolite compartmentalization Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b07819250cac40d8bbc977bfb407b14c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b07819250cac40d8bbc977bfb407b14c
record_format	dspace
spelling	oai:doaj.org-article:b07819250cac40d8bbc977bfb407b14c2021-11-15T15:56:46ZSelf-Protection against the Sphingolipid Biosynthesis Inhibitor Fumonisin B<sub>1</sub> Is Conferred by a <italic toggle="yes">FUM</italic> Cluster-Encoded Ceramide Synthase10.1128/mBio.00455-202150-7511https://doaj.org/article/b07819250cac40d8bbc977bfb407b14c2020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00455-20https://doaj.org/toc/2150-7511ABSTRACT Fumonisin (FB) mycotoxins produced by species of the genus Fusarium detrimentally affect human and animal health upon consumption, due to the inhibition of ceramide synthase. In the present work, we set out to identify mechanisms of self-protection employed by the FB1 producer Fusarium verticillioides. FB1 biosynthesis was shown to be compartmentalized, and two cluster-encoded self-protection mechanisms were identified. First, the ATP-binding cassette transporter Fum19 acts as a repressor of the FUM gene cluster. Appropriately, FUM19 deletion and overexpression increased and decreased, respectively, the levels of intracellular and secreted FB1. Second, the cluster genes FUM17 and FUM18 were shown to be two of five ceramide synthase homologs in Fusarium verticillioides, grouping into the two clades CS-I and CS-II in a phylogenetic analysis. The ability of FUM18 to fully complement the yeast ceramide synthase null mutant LAG1/LAC1 demonstrated its functionality, while coexpression of FUM17 and CER3 partially complemented, likely via heterodimer formation. Cell viability assays revealed that Fum18 contributes to the fungal self-protection against FB1 and increases resistance by providing FUM cluster-encoded ceramide synthase activity. IMPORTANCE The biosynthesis of fungal natural products is highly regulated not only in terms of transcription and translation but also regarding the cellular localization of the biosynthetic pathway. In all eukaryotes, the endoplasmic reticulum (ER) is involved in the production of organelles, which are subject to cellular traffic or secretion. Here, we show that in Fusarium verticillioides, early steps in fumonisin production take place in the ER, together with ceramide biosynthesis, which is targeted by the mycotoxin. A first level of self-protection is given by the presence of a FUM cluster-encoded ceramide synthase, Fum18, hitherto uncharacterized. In addition, the final fumonisin biosynthetic step occurs in the cytosol and is thereby spatially separate from the fungal ceramide synthases. We suggest that these strategies help the fungus to avoid self-poisoning during mycotoxin production.Slavica JanevskaIuliia FerlingKatarina JojićJulia RautschekSandra HoefgenRobert H. ProctorFalk HillmannVito ValianteAmerican Society for MicrobiologyarticleFusariumfumonisin B1ceramide synthaseABC transportermetabolite compartmentalizationMicrobiologyQR1-502ENmBio, Vol 11, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Fusarium fumonisin B1 ceramide synthase ABC transporter metabolite compartmentalization Microbiology QR1-502
spellingShingle	Fusarium fumonisin B1 ceramide synthase ABC transporter metabolite compartmentalization Microbiology QR1-502 Slavica Janevska Iuliia Ferling Katarina Jojić Julia Rautschek Sandra Hoefgen Robert H. Proctor Falk Hillmann Vito Valiante Self-Protection against the Sphingolipid Biosynthesis Inhibitor Fumonisin B<sub>1</sub> Is Conferred by a <italic toggle="yes">FUM</italic> Cluster-Encoded Ceramide Synthase
description	ABSTRACT Fumonisin (FB) mycotoxins produced by species of the genus Fusarium detrimentally affect human and animal health upon consumption, due to the inhibition of ceramide synthase. In the present work, we set out to identify mechanisms of self-protection employed by the FB1 producer Fusarium verticillioides. FB1 biosynthesis was shown to be compartmentalized, and two cluster-encoded self-protection mechanisms were identified. First, the ATP-binding cassette transporter Fum19 acts as a repressor of the FUM gene cluster. Appropriately, FUM19 deletion and overexpression increased and decreased, respectively, the levels of intracellular and secreted FB1. Second, the cluster genes FUM17 and FUM18 were shown to be two of five ceramide synthase homologs in Fusarium verticillioides, grouping into the two clades CS-I and CS-II in a phylogenetic analysis. The ability of FUM18 to fully complement the yeast ceramide synthase null mutant LAG1/LAC1 demonstrated its functionality, while coexpression of FUM17 and CER3 partially complemented, likely via heterodimer formation. Cell viability assays revealed that Fum18 contributes to the fungal self-protection against FB1 and increases resistance by providing FUM cluster-encoded ceramide synthase activity. IMPORTANCE The biosynthesis of fungal natural products is highly regulated not only in terms of transcription and translation but also regarding the cellular localization of the biosynthetic pathway. In all eukaryotes, the endoplasmic reticulum (ER) is involved in the production of organelles, which are subject to cellular traffic or secretion. Here, we show that in Fusarium verticillioides, early steps in fumonisin production take place in the ER, together with ceramide biosynthesis, which is targeted by the mycotoxin. A first level of self-protection is given by the presence of a FUM cluster-encoded ceramide synthase, Fum18, hitherto uncharacterized. In addition, the final fumonisin biosynthetic step occurs in the cytosol and is thereby spatially separate from the fungal ceramide synthases. We suggest that these strategies help the fungus to avoid self-poisoning during mycotoxin production.
format	article
author	Slavica Janevska Iuliia Ferling Katarina Jojić Julia Rautschek Sandra Hoefgen Robert H. Proctor Falk Hillmann Vito Valiante
author_facet	Slavica Janevska Iuliia Ferling Katarina Jojić Julia Rautschek Sandra Hoefgen Robert H. Proctor Falk Hillmann Vito Valiante
author_sort	Slavica Janevska
title	Self-Protection against the Sphingolipid Biosynthesis Inhibitor Fumonisin B<sub>1</sub> Is Conferred by a <italic toggle="yes">FUM</italic> Cluster-Encoded Ceramide Synthase
title_short	Self-Protection against the Sphingolipid Biosynthesis Inhibitor Fumonisin B<sub>1</sub> Is Conferred by a <italic toggle="yes">FUM</italic> Cluster-Encoded Ceramide Synthase
title_full	Self-Protection against the Sphingolipid Biosynthesis Inhibitor Fumonisin B<sub>1</sub> Is Conferred by a <italic toggle="yes">FUM</italic> Cluster-Encoded Ceramide Synthase
title_fullStr	Self-Protection against the Sphingolipid Biosynthesis Inhibitor Fumonisin B<sub>1</sub> Is Conferred by a <italic toggle="yes">FUM</italic> Cluster-Encoded Ceramide Synthase
title_full_unstemmed	Self-Protection against the Sphingolipid Biosynthesis Inhibitor Fumonisin B<sub>1</sub> Is Conferred by a <italic toggle="yes">FUM</italic> Cluster-Encoded Ceramide Synthase
title_sort	self-protection against the sphingolipid biosynthesis inhibitor fumonisin b<sub>1</sub> is conferred by a <italic toggle="yes">fum</italic> cluster-encoded ceramide synthase
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/b07819250cac40d8bbc977bfb407b14c
work_keys_str_mv	AT slavicajanevska selfprotectionagainstthesphingolipidbiosynthesisinhibitorfumonisinbsub1subisconferredbyaitalictoggleyesfumitalicclusterencodedceramidesynthase AT iuliiaferling selfprotectionagainstthesphingolipidbiosynthesisinhibitorfumonisinbsub1subisconferredbyaitalictoggleyesfumitalicclusterencodedceramidesynthase AT katarinajojic selfprotectionagainstthesphingolipidbiosynthesisinhibitorfumonisinbsub1subisconferredbyaitalictoggleyesfumitalicclusterencodedceramidesynthase AT juliarautschek selfprotectionagainstthesphingolipidbiosynthesisinhibitorfumonisinbsub1subisconferredbyaitalictoggleyesfumitalicclusterencodedceramidesynthase AT sandrahoefgen selfprotectionagainstthesphingolipidbiosynthesisinhibitorfumonisinbsub1subisconferredbyaitalictoggleyesfumitalicclusterencodedceramidesynthase AT roberthproctor selfprotectionagainstthesphingolipidbiosynthesisinhibitorfumonisinbsub1subisconferredbyaitalictoggleyesfumitalicclusterencodedceramidesynthase AT falkhillmann selfprotectionagainstthesphingolipidbiosynthesisinhibitorfumonisinbsub1subisconferredbyaitalictoggleyesfumitalicclusterencodedceramidesynthase AT vitovaliante selfprotectionagainstthesphingolipidbiosynthesisinhibitorfumonisinbsub1subisconferredbyaitalictoggleyesfumitalicclusterencodedceramidesynthase
_version_	1718427113594290176

Self-Protection against the Sphingolipid Biosynthesis Inhibitor Fumonisin B<sub>1</sub> Is Conferred by a <italic toggle="yes">FUM</italic> Cluster-Encoded Ceramide Synthase

Ejemplares similares