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Lookup NU author(s): Lina Mardiana, Alexandra Longcake, Dr Michael HallORCiD, Professor Mike ProbertORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Verticillins, epipolythiodioxopiperazine alkaloids that were first described over 50 years ago, have undergone extensive cytotoxic and pharmacological evaluations over the last decade. However, of the 27 verticillin analogues in the literature, the chemistry of verticillin D, which has two additional secondary hydroxy moieties, relative to verticillin A, has remained largely unexplored since its discovery in 1999. With the goal of advancing our understanding of verticillin D, there were three main objectives with this study: improving production, streamlining purification, and assigning absolute configuration via X-ray crystallography. To begin, the production of verticillin D was analyzed across seven fungal strains, and the top producer was further assessed under two fermentation conditions. Clonostachys rosea (strain MSX51257) biosynthesized the highest amount of verticillin D, with production peaking between 15-25 days on rice media. Interestingly, in contrast to similar studies that yield verticillin A, the biosynthesis of verticillin D was not accompanied by a suite of structurally related verticillin analogues. As such, the purification of verticillin D was more rapid and could be accomplished without the use of HPLC. These materials were used, in part, to determine the absolute configuration of verticillin D via X-ray crystallography, allowing for assignment of the asymmetric centers at both the 13 and 13′ positions as R, which has never been accomplished. This is only the third report of an X-ray structure of a verticillin analogue.
Author(s): Pierre HC, Patel DJ, Raja HA, Darveaux BA, Patel KI, Mardiana L, Longcake A, Hall MJ, Probert MR, Pearce CJ, Oberlies NA
Publication type: Article
Publication status: Published
Journal: Phytochemistry
Year: 2025
Volume: 236
Print publication date: 01/08/2025
Online publication date: 25/03/2025
Acceptance date: 25/03/2025
Date deposited: 31/03/2025
ISSN (print): 0031-9422
ISSN (electronic): 1873-3700
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.phytochem.2025.114492
DOI: 10.1016/j.phytochem.2025.114492
Data Access Statement: The crystal structure is deposited in CCDC 2376507
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