Notoamide R; a prominent diketopiperazine fermentation metabolite amongst others of Aspergillus ochraceus in the absence of ochratoxins
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Published version
Author(s)
Mantle, Peter
Roberts, Andrew
Beaumont, Claire
Type
Journal Article
Abstract
Ochratoxin A is historically the most notable secondary metabolite of Aspergillus ochraceus on account of its toxicity to animals and fish. Currently, over 150 compounds of diverse structure and biosynthesis is a challenge to predict the array for any particular isolate. Brief focus 30 years ago on its failure to produce ochratoxins on foods in Europe and USA revealed consistent failure to produce ochratoxin A by isolates from some USA beans. Analysis for familiar or nov-el metabolites particularly focused on a compound for which Mass and NMR analyses were in-conclusive. Resort to 14C -labelled biosynthetic precursors, particularly phenylalanine, to search for any close alternative to ochratoxins, was combined with conventional shredded wheat-shaken flask fermentation. This yielded, for an extract, an autoradiograph of a prepara-tive silica-gel chromatogram, subsequently analysed for an excised fraction by spectroscopic methodologies. Circumstances then delayed progress for many years until the present collabo-ration revealed it as notoamide R. Meanwhile pharmaceutical discovery around the turn of the millennium revealed stephacidins and notoamides, biosynthetically combining indole, iso-prenyl and diketopiperazine components. Later, in Japan, notoamide R was added as a me-tabolite of an Aspergillus sp., isolated from a marine mussel and the compound recovered from 1800 petri-dish fermentations. Renewed attention to our former studies in England has since shown for the first time that notoamide R can be a prominent metabolite of an A. ochraceus, sourced from a single shredded wheat flask culture with structure confirmed by spectroscopic data, and in the absence of ochratoxins. Renewed attention to the archived autoradiographed chromatogram allowed further exploration, but has particularly stimulated a fundamental bio-synthetic approach to considering influences redirecting intermediary metabolism to secondary metabolite accumulation.
Date Acceptance
2023-03-30
Citation
Molecules, 28 (8), pp.1-9
ISSN
1420-3049
Publisher
MDPI AG
Start Page
1
End Page
9
Journal / Book Title
Molecules
Volume
28
Issue
8
Copyright Statement
© 2023 by the authors. 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/).
Identifier
https://www.mdpi.com/1420-3049/28/8/3518
Publication Status
Published
Article Number
3518
Date Publish Online
2023-04-17