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Phenylacetyl pepstatin inhibitors of aspartyl proteases from Streptomyces varsoviensis

Abstract

A new pepstatin with a phenylacetyl group, pepstatin Pa (1), and its methyl ester (2) were isolated from Streptomyces varsoviensis DSM 40346. Their structures were determined by high-resolution mass spectrometry and nuclear magnetic resonance techniques. The absolute configuration was determined using the Marfey’s method. Both pentapeptide products are inhibitors of pepsin and cathepsin D. Interestingly, the bacterial genome contains no biosynthetic gene cluster for the new pepstatin, suggesting an extrachromosomal origin of the biosynthetic genes.

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Acknowledgements

This work was financially supported by the Collaborative Research Fund C6026-19G from the Research Grants Council of the HKSAR Government.

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Correspondence to Zhihong Guo.

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Ye, W., Guo, Z. Phenylacetyl pepstatin inhibitors of aspartyl proteases from Streptomyces varsoviensis. J Antibiot 75, 519–522 (2022). https://doi.org/10.1038/s41429-022-00542-6

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