The chromomycin CmmA acetyltransferase: a membrane-bound enzyme as a tool for increasing structural diversity of the antitumour mithramycin
Article first published online: 18 NOV 2010
© 2010 The Authors. Journal compilation © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd
Special Issue: Crystal ball and Streptomyces Special issue. Guest Editors: Hildgund Schrempf, Paul Dyson and Sergey Zotchev
Volume 4, Issue 2, pages 226–238, March 2011
How to Cite
García, B., González-Sabín, J., Menéndez, N., Braña, A. F., Núñez, L. E., Morís, F., Salas, J. A. and Méndez, C. (2011), The chromomycin CmmA acetyltransferase: a membrane-bound enzyme as a tool for increasing structural diversity of the antitumour mithramycin. Microbial Biotechnology, 4: 226–238. doi: 10.1111/j.1751-7915.2010.00229.x
- Issue published online: 22 FEB 2011
- Article first published online: 18 NOV 2010
- Received 11 June, 2010; accepted 24 September, 2010.
Mithramycin and chromomycin A3 are two structurally related antitumour compounds, which differ in the glycosylation profiles and functional group substitutions of the sugars. Chromomycin contains two acetyl groups, which are incorporated during the biosynthesis by the acetyltransferase CmmA in Streptomyces griseus ssp. griseus. A bioconversion strategy using an engineered S. griseus strain generated seven novel acetylated mithramycins. The newly formed compounds were purified and characterized by MS and NMR. These new compounds differ from their parental compounds in the presence of one, two or three acetyl groups, attached at 3E, 4E and/or 4D positions. All new mithramycin analogues showed antitumour activity at micromolar of lower concentrations. Some of the compounds showed improved activities against glioblastoma or pancreas tumour cells. The CmmA acetyltransferase was located in the cell membrane and was shown to accept several acyl-CoA substrates. All these results highlight the potential of CmmA as a tool to create structural diversity in these antitumour compounds.