Cytochrome P450 oxidase SlgO1 catalyzes the biotransformation of tirandamycin C to a new tirandamycin derivative
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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.
KeywordsTirandamycins Streptolydigin Cytochrome P450 oxidase SlgO1 Combinatorial biosynthesis
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).
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Conflict of interest
All the authors declare no conflict of interest with respect to this paper.
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