Applied Biochemistry and Biotechnology

, Volume 184, Issue 4, pp 1404–1420 | Cite as

Substrate Scope of O-Methyltransferase from Streptomyces peucetius for Biosynthesis of Diverse Natural Products Methoxides

  • Prakash Parajuli
  • Ramesh Prasad Pandey
  • Thi Huyen Trang Nguyen
  • Dipesh Dhakal
  • Jae Kyung Sohng
Article

Abstract

Methylation is a common post-modification reaction that is observed during the biosynthesis of secondary metabolites produced by plants and microorganisms. Based on the sequence information from Streptomyces peucetius ATCC27952, a putative O-methyltransferase (OMT) gene SpOMT7740 was polymerase chain reaction amplified and cloned into E. coli BL21 (DE3) host to test the substrate promiscuity and conduct functional characterization. In vitro and in vivo reaction assays were carried out over various classes of substrates: flavonoids (flavonol, flavones, and isoflavonoid), chalcones, anthraquinones, anthracyclines, and sterol molecules, and the applications in synthesizing diverse classes of O-methoxy natural products were also illustrated. SpOMT7740 catalyzed the O-methylation reaction to form various natural and non-natural O-methoxides, includes 7-hydroxy-8-O-methoxy flavone, 3-O-methoxy flavone, three mono-, di-, and tri-O-methoxy genistein, mono-O-methoxy phloretin, mono-O-methoxy luteolin, 3-O-methoxy β-sitosterol, and O-methoxy anthraquinones (emodin and aloe emodin) and O-methoxy anthracycline (daunorubicin) exhibiting diverse substrate flexibility. Daunorubicin is a native secondary metabolite of S. peucetius. Among the compounds tested, 7,8-dihydroxyflavone was the best substrate for bioconversion to 7-hydroxy-8-O-methoxy flavone, and it was structurally elucidated. This enzyme showed a flexible catalysis over the given ranges of temperature, pH, and divalent cationic conditions for O-methylation.

Keywords

O-methyltransferase SpOMT7740 Streptomyces Methylated natural products Substrate flexibility 

Notes

Funding Information

This work was supported by a grant from the Next-Generation BioGreen 21 Program (SSAC, grant no.: PJ01111901), Rural Development Administration, Republic of Korea.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interests.

Supplementary material

12010_2017_2603_MOESM1_ESM.docx (1.5 mb)
ESM 1 (DOCX 1567 kb)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Life Science and Biochemical EngineeringSun Moon UniversityAsan-siRepublic of Korea
  2. 2.Department of BT-Convergent Pharmaceutical EngineeringSun Moon UniversityAsan-siRepublic of Korea

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