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3 Biotech

, 9:71 | Cite as

Cytochrome P450 oxidase SlgO1 catalyzes the biotransformation of tirandamycin C to a new tirandamycin derivative

  • Xuhua MoEmail author
  • Chun Gui
  • Song Yang
Original Article
  • 12 Downloads

Abstract

In the present study, an Escherichia coli whole cell system with overexpression of a cytochrome P450 oxidase SlgO1 involved in streptolydigin biosynthetic pathway, an E. coli flavodoxin NADP+ oxidoreductase (EcFLDR), and an E. coli flavodoxin A (EcFLDA) were constructed. Biotransformation experiments revealed that SlgO1 can convert tirandamycin C to tirandamycin F, indicating that it can introduce a hydroxyl group into the C-10 position of tirandamycin C. Subsequently, slgO1 was cloned into pSET152AKE vector under the downstream of ermE* promoter, which was, respectively, introduced into Streptomyces sp. SCSIO1666 (tirandamycin B producer), Streptomyces sp. Ju1008 (tirandamycin C producer), and Streptomyces sp. Ju1009 (tirandamycin E producer). A novel tirandamycin derivative tirandamycin L accumulated in the engineered strain Streptomyces sp. Ju1008::slgO1 was isolated and its structure was determined on the basis of nuclear magnetic resonance (NMR) and mass spectrometry. Unlike most of the identified tirandamycins, tirandamycin L possessed a rare C-11–C-12 saturated bond as well as a C-10 ketone moiety. In addition, tirandamycin L showed weaker antibacterial activity. Based on the structure of tirandamycin L, SlgO1 was proposed to be responsible for multiple modifications toward tirandamycin C, including the formation of C-10 hydroxyl and C-11–C-12 saturated bond.

Keywords

Tirandamycins Streptolydigin Cytochrome P450 oxidase SlgO1 Combinatorial biosynthesis 

Notes

Acknowledgements

We are very grateful to Professor Jianhua Ju for providing the tirandamycin-producing strains. Research in this work was supported by Natural Science Foundation of Shandong Province (No. ZR2013CL020) and Research Foundation for Advanced Talents of Qingdao Agricultural University (No. 631301).

Compliance with ethical standards

Conflict of interest

All the authors declare no conflict of interest with respect to this paper.

Supplementary material

13205_2019_1611_MOESM1_ESM.docx (807 kb)
Supplementary material 1 (DOCX 806 KB)

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Copyright information

© King Abdulaziz City for Science and Technology 2019

Authors and Affiliations

  1. 1.Shandong Province Key Laboratory of Applied Mycology, School of Life SciencesQingdao Agricultural UniversityQingdaoChina
  2. 2.CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of OceanologyChinese Academy of SciencesGuangzhouChina

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