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Thielavins: tuned biosynthesis and LR-HSQMBC for structure elucidation

The Journal of Antibiotics volume 74, pages 300–306 (2021)Cite this article

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Abstract

A series of thielavins I, V, and Q (1–3) and the previously undescribed thielavin Z8 (4) were isolated from cultures of a fungal Shiraia-like sp. (strain MSX60519) that were grown under a suite of media and light conditions, with enhanced biosynthesis noted using rice as a substrate with 12:12 h light:dark cycles. Conversely, oatmeal medium and continuous white light-emitting diode light exposure negatively affected the production of these compounds, at least by strain MSX60519. The structure of 4 was determined using NMR spectroscopic data and mass fragmentation patterns. Of note, the utility of LR-HSQMBC and NOESY NMR experiments in the structural elucidation of these hydrogen-deficient natural products was demonstrated. Compounds 1–4 exhibited cytotoxic activity at the micromolar level against human breast, ovarian, and melanoma cancer cell lines.

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Data availability

1H NMR, 13C NMR and (+)-HRESIMS data for compounds 1–4. 2D NMR data (HSQC and HMBC) for the new compound (4). MS fragmentation patterns of 1–4. LR-HSQMBC NMR for 1 & 4 and NOESY NMR for 3 & 4. The 1D and 2D NMR spectra for 1–4 were deposited in Harvard Dataverse and can be freely accessed through https://doi.org/10.7910/DVN/QF3WOJ.

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Acknowledgements

This research was supported by the National Institutes of Health via the National Cancer Institute (P01 CA125066). We thank Dr Tamam El-Elimat, Dr Laura Flores-Bocanegra, and Tyler Graf for helpful suggestions.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA

    Zeinab Y. Al Subeh, Huzefa A. Raja & Nicholas H. Oberlies

  2. Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL, USA

    Amanda Maldonado & Joanna E. Burdette

  3. Mycosynthetix, Inc., Hillsborough, NC, USA

    Cedric J. Pearce

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  1. Zeinab Y. Al Subeh
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  2. Huzefa A. Raja
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  6. Nicholas H. Oberlies
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Correspondence to Nicholas H. Oberlies.

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NHO declares that he is a member of the Scientific Advisory Board of Mycosynthetix, Inc.

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Al Subeh, Z.Y., Raja, H.A., Maldonado, A. et al. Thielavins: tuned biosynthesis and LR-HSQMBC for structure elucidation. J Antibiot 74, 300–306 (2021). https://doi.org/10.1038/s41429-021-00405-6

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