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In vivo investigation of the role of SfmO2 in saframycin A biosynthesis by structural characterization of the analogue saframycin O

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Abstract

Saframycin A (SFM-A), a tetrahydroisoquinoline antibiotic isolated from Streptomyces lavendulae, shows potent anti-proliferation activities against a variety of tumor cell lines, and shares the core structure with ecteinascidin 743 (ET-743), the anticancer drug for soft-tissue sarcoma. Characterization of the SFM-A biosynthetic gene cluster revealed three nonribosomal peptide synthetase genes and a series of genes encoding oxygenases. To investigate the function of sfmO2 gene, encoding a FAD-dependent monooxygenase/hydroxylase, we constructed the gene replacement mutant (sfmO2) strain S. lavendulae TL2007 and the corresponding gene complementation mutant strain S. lavendulae TL2008. A novel compound, SFM-O, was isolated from the sfmO2 replacement mutant strain and its structure was characterized by comparison to the HRMS and NMR spectra of SFM-A. These findings indicated that SfmO2 is responsible for the oxidation of ring A in the biosynthetic pathway of SFM-A, and the new compound SFM-O could be considered as an advanced intermediate in the semisynthesis of ET-743.

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Authors and Affiliations

  1. State Key Laboratory of Bio-organic and Natural Products Chemistry; Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, China

    Chao Peng, Yu-Min Tang, Lei Li, Wei Ding, Wei Deng, Jin-Yue Pu, Wen Liu & Gong-Li Tang

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  1. Chao Peng
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  2. Yu-Min Tang
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  3. Lei Li
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  4. Wei Ding
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  7. Wen Liu
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  8. Gong-Li Tang
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Correspondence to Gong-Li Tang.

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Peng, C., Tang, YM., Li, L. et al. In vivo investigation of the role of SfmO2 in saframycin A biosynthesis by structural characterization of the analogue saframycin O. Sci. China Chem. 55, 90–97 (2012). https://doi.org/10.1007/s11426-011-4450-4

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  • DOI: https://doi.org/10.1007/s11426-011-4450-4

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