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A carbonate-forming Baeyer-Villiger monooxygenase

Nature Chemical Biology volume 10, pages 552–554 (2014)Cite this article

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Abstract

Despite the remarkable versatility displayed by flavin-dependent monooxygenases (FMOs) in natural product biosynthesis, one notably missing activity is the oxidative generation of carbonate functional groups. We describe a multifunctional Baeyer-Villiger monooxygenase, CcsB, which catalyzes the formation of an in-line carbonate in the macrocyclic portion of cytochalasin E. This study expands the repertoire of activities of FMOs and provides a possible synthetic strategy for transformation of ketones into carbonates.

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Figure 1: Cytochalasins with different oxidation outcomes in the macrocyclic portion.
Figure 2: Genetic confirmation of CcsB activity.
Figure 3: Reactions catalyzed by CcsB and chemical complementation of ΔccsB-37.

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Acknowledgements

This work was supported by the US National Institutes of Health (1R01GM085128 and 1DP1GM106413) to Y.T., the Natural Sciences and Engineering Research Council of Canada and the Canada Research Chair in Bioorganic and Medicinal Chemistry to J.C.V. and the US National Science Foundation (NSF) CHE-1059084 to K.N.H. A.P. thanks the Chemistry Biology Interface program (T32GM008496) for support. NMR instrumentation was supported by the NSF equipment grant CHE-1048804. We thank Y.-H. Chooi and N.K. Garg for helpful discussions. We thank S.I. Khan at the University of California–Los Angeles Department of Chemistry and Biochemistry crystallography facility for solving the X-ray structures. We thank D. Li at Chinese Ocean University for providing the standards for 5, 9 and 10. We acknowledge the Extreme Science and Engineering Design Environment program (TG-CHE040013N) for providing high-performance computing resources.

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Author notes

  1. Wen-Bing Yin

    Present address: Present address: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.,

Authors and Affiliations

  1. Department of Chemical and Biomolecular Engineering, University of California–Los Angeles, Los Angeles, California, USA

    Youcai Hu, Wei Xu, Jingjing Wang, Wen-Bing Yin, Kangjian Qiao & Yi Tang

  2. Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada

    David Dietrich, Justin A J Thuss & John C Vederas

  3. Department of Chemistry and Biochemistry, University of California–Los Angeles, Los Angeles, California, USA

    Ashay Patel, K N Houk & Yi Tang

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  1. Youcai Hu
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Contributions

Y.H., D.D., J.C.V. and Y.T. developed the hypothesis and designed the study. D.D. performed the isotopic labeling studies in A. clavatus, and J.A.J.T. and D.D. prepared selected substrate analogs. Y.H. performed the compound isolation and characterization. Y.H. performed the in vitro analysis of CcsB functions. A.P. and K.N.H. performed and interpreted the density functional theory calculations. All of the authors analyzed and discussed the results. Y.H., J.C.V. and Y.T. prepared the manuscript.

Corresponding authors

Correspondence to John C Vederas or Yi Tang.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Results, Supplementary Tables 1–7, Supplementary Figures 1–33 and Supplementary Notes 1–3. (PDF 16669 kb)

Supplementary Data Set 1

CIF file for the crystal structure of cytochalasin Z16 (9), CCDC 970432 (TXT 591 kb)

Supplementary Data Set 2

CIF file for the crystal structure of ketocytochalasin (7), CCDC 970431 (TXT 933 kb)

Supplementary Data Set 3

Checkcif output file for CIF file of 9. (PDF 214 kb)

Supplementary Data Set 4

Checkcif output file for CIF file of 7. (PDF 231 kb)

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Cite this article

Hu, Y., Dietrich, D., Xu, W. et al. A carbonate-forming Baeyer-Villiger monooxygenase. Nat Chem Biol 10, 552–554 (2014). https://doi.org/10.1038/nchembio.1527

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