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Identification of Gene Biomarkers for Tigilanol Tiglate Content in Fontainea picrosperma

Tigilanol tiglate (EBC-46) is a small-molecule natural product under development for the treatment of cancers in humans and companion animals. The drug is currently produced by purification from the Australian rainforest tree Fontainea picrosperma (Euphorbiaceae). As part of a selective-breeding pro...

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Autores principales: Mitu, Shahida A, Stewart, Praphaporn, Tran, Trong D, Reddell, Paul W, Cummins, Scott F, Ogbourne, Steven M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268252/
https://www.ncbi.nlm.nih.gov/pubmed/35807225
http://dx.doi.org/10.3390/molecules27133980
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author Mitu, Shahida A
Stewart, Praphaporn
Tran, Trong D
Reddell, Paul W
Cummins, Scott F
Ogbourne, Steven M.
author_facet Mitu, Shahida A
Stewart, Praphaporn
Tran, Trong D
Reddell, Paul W
Cummins, Scott F
Ogbourne, Steven M.
author_sort Mitu, Shahida A
collection PubMed
description Tigilanol tiglate (EBC-46) is a small-molecule natural product under development for the treatment of cancers in humans and companion animals. The drug is currently produced by purification from the Australian rainforest tree Fontainea picrosperma (Euphorbiaceae). As part of a selective-breeding program to increase EBC-46 yield from F. picrosperma plantations, we investigated potential gene biomarkers associated with biosynthesis of EBC-46. Initially, we identified individual plants that were either high (>0.039%) or low EBC-46 (<0.008%) producers, then assessed their differentially expressed genes within the leaves and roots of these two groups by quantitative RNA sequencing. Compared to low EBC-46 producers, high-EBC-46-producing plants were found to have 145 upregulated genes and 101 downregulated genes in leaves and 53 upregulated genes and 82 downregulated genes in roots. Most of these genes were functionally associated with defence, transport, and biosynthesis. Genes identified as expressed exclusively in either the high or low EBC-46-producing plants were further validated by quantitative PCR, showing that cytochrome P450 94C1 in leaves and early response dehydration 7.1 and 2-alkenal reductase in roots were consistently and significantly upregulated in high-EBC-46 producers. In summary, this study has identified biomarker genes that may be used in the selective breeding of F. picrosperma.
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spelling pubmed-92682522022-07-09 Identification of Gene Biomarkers for Tigilanol Tiglate Content in Fontainea picrosperma Mitu, Shahida A Stewart, Praphaporn Tran, Trong D Reddell, Paul W Cummins, Scott F Ogbourne, Steven M. Molecules Article Tigilanol tiglate (EBC-46) is a small-molecule natural product under development for the treatment of cancers in humans and companion animals. The drug is currently produced by purification from the Australian rainforest tree Fontainea picrosperma (Euphorbiaceae). As part of a selective-breeding program to increase EBC-46 yield from F. picrosperma plantations, we investigated potential gene biomarkers associated with biosynthesis of EBC-46. Initially, we identified individual plants that were either high (>0.039%) or low EBC-46 (<0.008%) producers, then assessed their differentially expressed genes within the leaves and roots of these two groups by quantitative RNA sequencing. Compared to low EBC-46 producers, high-EBC-46-producing plants were found to have 145 upregulated genes and 101 downregulated genes in leaves and 53 upregulated genes and 82 downregulated genes in roots. Most of these genes were functionally associated with defence, transport, and biosynthesis. Genes identified as expressed exclusively in either the high or low EBC-46-producing plants were further validated by quantitative PCR, showing that cytochrome P450 94C1 in leaves and early response dehydration 7.1 and 2-alkenal reductase in roots were consistently and significantly upregulated in high-EBC-46 producers. In summary, this study has identified biomarker genes that may be used in the selective breeding of F. picrosperma. MDPI 2022-06-21 /pmc/articles/PMC9268252/ /pubmed/35807225 http://dx.doi.org/10.3390/molecules27133980 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mitu, Shahida A
Stewart, Praphaporn
Tran, Trong D
Reddell, Paul W
Cummins, Scott F
Ogbourne, Steven M.
Identification of Gene Biomarkers for Tigilanol Tiglate Content in Fontainea picrosperma
title Identification of Gene Biomarkers for Tigilanol Tiglate Content in Fontainea picrosperma
title_full Identification of Gene Biomarkers for Tigilanol Tiglate Content in Fontainea picrosperma
title_fullStr Identification of Gene Biomarkers for Tigilanol Tiglate Content in Fontainea picrosperma
title_full_unstemmed Identification of Gene Biomarkers for Tigilanol Tiglate Content in Fontainea picrosperma
title_short Identification of Gene Biomarkers for Tigilanol Tiglate Content in Fontainea picrosperma
title_sort identification of gene biomarkers for tigilanol tiglate content in fontainea picrosperma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268252/
https://www.ncbi.nlm.nih.gov/pubmed/35807225
http://dx.doi.org/10.3390/molecules27133980
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