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Thielavins: tuned biosynthesis and LR-HSQMBC for structure elucidation


A series of thielavins I, V, and Q (13) 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 14 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 14. 2D NMR data (HSQC and HMBC) for the new compound (4). MS fragmentation patterns of 14. LR-HSQMBC NMR for 1 & 4 and NOESY NMR for 3 & 4. The 1D and 2D NMR spectra for 14 were deposited in Harvard Dataverse and can be freely accessed through


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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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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).

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