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Structure Revision of Penipacids A–E Reveals a Putative New Cryptic Natural Product, N-aminoanthranilic Acid, with Potential as a Transcriptional Regulator of Silent Secondary Metabolism

Reconsideration of the spectroscopic data for penipacids A–E, first reported in 2013 as the acyclic amidines 1–5 from the South China deep sea sediment-derived fungus Penicillium paneum SD-44, prompted a total synthesis structure revision as the hydrazones 6–10. This revision strongly supported the...

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Autores principales: Khalil, Zeinab G., Kankanamge, Sarani, Capon, Robert J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225364/
https://www.ncbi.nlm.nih.gov/pubmed/35736142
http://dx.doi.org/10.3390/md20060339
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author Khalil, Zeinab G.
Kankanamge, Sarani
Capon, Robert J.
author_facet Khalil, Zeinab G.
Kankanamge, Sarani
Capon, Robert J.
author_sort Khalil, Zeinab G.
collection PubMed
description Reconsideration of the spectroscopic data for penipacids A–E, first reported in 2013 as the acyclic amidines 1–5 from the South China deep sea sediment-derived fungus Penicillium paneum SD-44, prompted a total synthesis structure revision as the hydrazones 6–10. This revision strongly supported the proposition that penipacids A–B (6–7) were artifact Schiff base adducts of the cryptic (undetected) natural product N-aminoanthranilic acid (11) with diacetone alcohol, induced by excessive exposure to acetone and methanol under acidic handling conditions. Likewise, the revised structures for penipacids C–D (8–9) and E (10) raise the possibility that they may also be artifact Schiff base adducts of 11 and the media constituents pyruvic acid and furfural, respectively. A review of the natural products literature revealed other Schiff base (hydrazone) natural products that might also be viewed as Schiff base adduct artifacts of 11. Having raised the prospect that 11 is an undetected and reactive cryptic natural product, we went on to establish that 11 is not cytotoxic to a range of bacterial, fungal or mammalian (human) cell types. Instead, when added as a supplement to microbial cultivations, 11 can act as a chemical cue/transcriptional regulator, activating and/or enhancing the yield of biosynthetic gene clusters encoding for other natural product chemical defenses. This study demonstrates the value of challenging the structure and artifact status of natural products, as a window into the hidden world of cryptic and highly reactive natural products.
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spelling pubmed-92253642022-06-24 Structure Revision of Penipacids A–E Reveals a Putative New Cryptic Natural Product, N-aminoanthranilic Acid, with Potential as a Transcriptional Regulator of Silent Secondary Metabolism Khalil, Zeinab G. Kankanamge, Sarani Capon, Robert J. Mar Drugs Article Reconsideration of the spectroscopic data for penipacids A–E, first reported in 2013 as the acyclic amidines 1–5 from the South China deep sea sediment-derived fungus Penicillium paneum SD-44, prompted a total synthesis structure revision as the hydrazones 6–10. This revision strongly supported the proposition that penipacids A–B (6–7) were artifact Schiff base adducts of the cryptic (undetected) natural product N-aminoanthranilic acid (11) with diacetone alcohol, induced by excessive exposure to acetone and methanol under acidic handling conditions. Likewise, the revised structures for penipacids C–D (8–9) and E (10) raise the possibility that they may also be artifact Schiff base adducts of 11 and the media constituents pyruvic acid and furfural, respectively. A review of the natural products literature revealed other Schiff base (hydrazone) natural products that might also be viewed as Schiff base adduct artifacts of 11. Having raised the prospect that 11 is an undetected and reactive cryptic natural product, we went on to establish that 11 is not cytotoxic to a range of bacterial, fungal or mammalian (human) cell types. Instead, when added as a supplement to microbial cultivations, 11 can act as a chemical cue/transcriptional regulator, activating and/or enhancing the yield of biosynthetic gene clusters encoding for other natural product chemical defenses. This study demonstrates the value of challenging the structure and artifact status of natural products, as a window into the hidden world of cryptic and highly reactive natural products. MDPI 2022-05-24 /pmc/articles/PMC9225364/ /pubmed/35736142 http://dx.doi.org/10.3390/md20060339 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
Khalil, Zeinab G.
Kankanamge, Sarani
Capon, Robert J.
Structure Revision of Penipacids A–E Reveals a Putative New Cryptic Natural Product, N-aminoanthranilic Acid, with Potential as a Transcriptional Regulator of Silent Secondary Metabolism
title Structure Revision of Penipacids A–E Reveals a Putative New Cryptic Natural Product, N-aminoanthranilic Acid, with Potential as a Transcriptional Regulator of Silent Secondary Metabolism
title_full Structure Revision of Penipacids A–E Reveals a Putative New Cryptic Natural Product, N-aminoanthranilic Acid, with Potential as a Transcriptional Regulator of Silent Secondary Metabolism
title_fullStr Structure Revision of Penipacids A–E Reveals a Putative New Cryptic Natural Product, N-aminoanthranilic Acid, with Potential as a Transcriptional Regulator of Silent Secondary Metabolism
title_full_unstemmed Structure Revision of Penipacids A–E Reveals a Putative New Cryptic Natural Product, N-aminoanthranilic Acid, with Potential as a Transcriptional Regulator of Silent Secondary Metabolism
title_short Structure Revision of Penipacids A–E Reveals a Putative New Cryptic Natural Product, N-aminoanthranilic Acid, with Potential as a Transcriptional Regulator of Silent Secondary Metabolism
title_sort structure revision of penipacids a–e reveals a putative new cryptic natural product, n-aminoanthranilic acid, with potential as a transcriptional regulator of silent secondary metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225364/
https://www.ncbi.nlm.nih.gov/pubmed/35736142
http://dx.doi.org/10.3390/md20060339
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