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Structural modification of herboxidiene by substrate-flexible cytochrome P450 and glycosyltransferase

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Abstract

Herboxidiene is a natural product produced by Streptomyces chromofuscus exhibiting herbicidal activity as well as antitumor properties. Using different substrate-flexible cytochrome P450s and glycosyltransferase, different novel derivatives of herboxidiene were generated with structural modifications by hydroxylation or epoxidation or conjugation with a glucose moiety. Moreover, two isomers of herboxidiene containing extra tetrahydrofuran or tetrahydropyran moiety in addition to the existing tetrahydropyran moiety were characterized. The hydroxylated products for both of these compounds were also isolated and characterized from S. chromofuscus PikC harboring pikC from the pikromycin gene cluster of Streptomyces venezuelae and S. chromofuscus EryF harboring eryF from the erythromycin gene cluster of Saccharopolyspora erythraea. The compounds generated were characterized by high-resolution quadrupole-time-of-flight electrospray ionization mass spectrometry (HR-QTOF-ESI/MS) and 1H- and 13C-nuclear magnetic resonance (NMR) analyses. The evaluation of antibacterial activity against three Gram-positive bacteria, Micrococcus luteus, Bacillus subtilis, and Staphylococcus aureus, indicated that modification resulted in a transition from anticancer to antibacterial potency.

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Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (NRF-2014R1A2A2A01002875).

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Authors and Affiliations

  1. Institute of Biomolecule Reconstruction (iBR), Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70, Sunmoon-Ro221, Tangjeong-myeon, Asan, Chungnam, 333-708, Republic of Korea

    Amit Kumar Jha, Dipesh Dhakal, Pham Thi Thuy Van, Anaya Raj Pokhrel, Tokutaro Yamaguchi, Hye Jin Jung & Jae Kyung Sohng

  2. Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, Republic of Korea

    Yeo Joon Yoon

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  1. Amit Kumar Jha
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  2. Dipesh Dhakal
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Correspondence to Jae Kyung Sohng.

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Jha, A.K., Dhakal, D., Van, P.T.T. et al. Structural modification of herboxidiene by substrate-flexible cytochrome P450 and glycosyltransferase. Appl Microbiol Biotechnol 99, 3421–3431 (2015). https://doi.org/10.1007/s00253-015-6431-6

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  • DOI: https://doi.org/10.1007/s00253-015-6431-6

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