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J Nat Prod. 2020 Mar 27;83(3):738-743. doi: 10.1021/acs.jnatprod.9b01237. Epub 2020 Feb 27.

The Chemistry and Biology of Bactobolin: A 10-Year Collaboration with Natural Product Chemist Extraordinaire Jon Clardy.

Author information

1
Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195, United States.
2
Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, United States.
3
Departments of Chemistry and Molecular Biology, Princeton University, Princeton, New Jersey 08544, United States.

Abstract

Bactobolin is a hybrid natural product with potent cytotoxic activity. Its production from Burkholderia thailandensis was reported as part of a collaboration between the Greenberg and Clardy laboratories in 2010. The collaboration sparked a series of studies leading to the discovery of new analogues and associated structure-activity relationships, the identification of the bactobolin biosynthetic gene cluster and assembly of its unusual amino acid building block, the molecular target of and resistance to the antibiotic, and finally an X-ray crystal structure of the ribosome-bactobolin complex. Herein, we review the collaborations that led to our current understanding of the chemistry and biology of bactobolin.

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