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Production of a hybrid 16-membered macrolide antibiotic by genetic engineering of Micromonospora sp. TPMA0041

  • Metabolic Engineering and Synthetic Biology
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Some polyketide-derived bioactive compounds contain sugars attached to the aglycone core, and these sugars often enhance or impart specific biological activity to the molecule. Mycinamicin II, a 16-member macrolide antibiotic produced by Micromonospora griseorubida A11725, contains a branched lactone and two different deoxyhexose sugars, d-desosamine and d-mycinose, at the C-5 and C-21 positions, respectively. We previously engineered an expression plasmid pSETmycinose containing the d-mycinose biosynthesis genes from M. griseorubida A11725. This plasmid was introduced into Micromonospora sp. FERM BP-1076 cells, which produce the 16-membered macrolide antibiotic izenamicin. The resulting engineered strain TPMA0041 produced 23-O-mycinosyl-20-deoxy-izenamicin B1 and 22-O-mycinosyl-izenamicin B2. 23-O-mycinosyl-20-deoxy-izenamicin B1 has been produced by the engineered strain M. rosaria TPMA0001 containing pSETmycinose as 23-O-mycinosyl-20-deoxo-20-dihydro-12,13-deepoxyrosamicin (=IZI) in our recent study, and 22-O-mycinosyl-izenamicin B2 has previously been synthesized as a macrolide antibiotic TMC-016 with strong antibacterial activity. The production of 22-O-mycinosyl-izenamicin B2 (=TMC-016) was increased when propionate, a precursor of methylmalonyl-CoA, was added to the culture broth.

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Acknowledgments

We thank Dr. Shingo Fujisaki (Toho University) for help with LC–MS analysis, Dr. Wei Li (Toho University) for help with NMR analysis, and Ms. Yumi Ichikawa (Toho University) for help with antibacterial activity assay.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba, 274-8510, Japan

    Ayami Sakai, Aki Mitsumori, Mika Furukawa, Yojiro Anzai & Fumio Kato

  2. School of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Kyuban-cho, Koshien, Nishinomiya, 663-8179, Japan

    Kenji Kinoshita

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  1. Ayami Sakai
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  2. Aki Mitsumori
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  3. Mika Furukawa
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  6. Fumio Kato
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Correspondence to Yojiro Anzai.

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Sakai, A., Mitsumori, A., Furukawa, M. et al. Production of a hybrid 16-membered macrolide antibiotic by genetic engineering of Micromonospora sp. TPMA0041. J Ind Microbiol Biotechnol 39, 1693–1701 (2012). https://doi.org/10.1007/s10295-012-1173-2

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  • DOI: https://doi.org/10.1007/s10295-012-1173-2

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