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Laxaphycins B5 and B6 from the cultured cyanobacterium UIC 10484

The Journal of Antibiotics volume 73, pages 526–533 (2020)Cite this article

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Abstract

Two laxaphycin type-B cyclic dodecapeptides, laxaphycins B5 and B6, were obtained from UIC 10484, a freshwater cf. Phormidium sp. Analysis using the 16S rRNA sequence found UIC 10484 to clade with UIC 10045, a known laxaphycin type-A and -B producer, and MS/MS analysis revealed the presence of two novel laxaphycin type-B compounds. The structures of the metabolites were elucidated using 2D NMR and MS/MS. The absolute configurations of the amino acids were determined by advanced Marfey’s analysis. Both metabolites were evaluated against the same three cancer cell lines. The IC50 of both laxaphycins B5 and B6 was near 1 μM against breast cancer MDA-MB-231, melanoma MDA-MB-435, and ovarian cancer OVCAR3 cell lines.

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Acknowledgements

This research was supported by the NCI/NIH P01 CA12506 grant and The Office of the Director, NIH National Center for Complementary and Integrative Health (NCCIH) T32AT007533-05 training grant (PS). We thank Dr Jonathan Bisson and Dr Charlotte Simmer for their assistance using the Q-TOF mass spectrometer, Rojin Ahadi and Angel Antunez for isolating and culturing strain UIC 10484, Dr Ben Ramirez for his guidance using the UIC Center for Structure Biology NMR instrumentation, Dr Chen of the Research Resources Center’s Mass Spectrometry Core for use of the Agilent 6454 LC/Q-TOF, and Dr Young Jeong for access to their HPLC system. We’d also like to acknowledge the James R Fuchs lab of Ohio State University for synthesizing the NMeIle and 3OHLeu standards.

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  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, 60612, USA

    Peter Sullivan, Aleksej Krunic, Joanna E. Burdette & Jimmy Orjala

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  1. Peter Sullivan
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Correspondence to Jimmy Orjala.

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Dedicated to Professor William Fenical in recognition of his contributions to marine derived secondary metabolites

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Sullivan, P., Krunic, A., Burdette, J.E. et al. Laxaphycins B5 and B6 from the cultured cyanobacterium UIC 10484. J Antibiot 73, 526–533 (2020). https://doi.org/10.1038/s41429-020-0301-x

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