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A new mycinosyl rosamicin derivative produced by an engineered Micromonospora rosaria mutant with a cytochrome P450 gene disruption introducing the d-mycinose biosynthetic gene

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

Abstract

Genetic engineering of post-polyketide synthase-tailoring genes can be used to generate new macrolide analogs through manipulation of the genes involved in their biosynthesis. Rosamicin, a 16-member macrolide antibiotic produced by Micromonospora rosaria IFO13697, contains a formyl group and an epoxide at C-20 and C-12/13 positions which are formed by the cytochrome P450 enzymes RosC and RosD, respectively. The d-mycinose biosynthesis genes in mycinamicin II biosynthesis gene cluster of Micomonospora guriseorubida A11725 were introduced into the rosC and rosD disruption mutants of M. rosaria IFO13697. The resulting engineered strains, M. rosaria TPMA0054 and TPMA0069, produced mycinosyl rosamicin derivatives, IZIV and IZV, respectively. IZIV was identified as a novel mycinosyl rosamicin derivative, 23-O-mycinosyl-20-deoxo-20-dihydrorosamicin.

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Authors and Affiliations

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

    Yohei Iizaka, Noriko Higashi, Wei Li, Atsushi Fukumoto, Yojiro Anzai & Fumio Kato

Authors
  1. Yohei Iizaka
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  2. Noriko Higashi
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  3. Wei Li
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  4. Atsushi Fukumoto
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  5. Yojiro Anzai
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  6. Fumio Kato
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Corresponding author

Correspondence to Yojiro Anzai.

Additional information

Y. Iizaka and N. Higashi contributed equally to this work.

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Iizaka, Y., Higashi, N., Li, W. et al. A new mycinosyl rosamicin derivative produced by an engineered Micromonospora rosaria mutant with a cytochrome P450 gene disruption introducing the d-mycinose biosynthetic gene. J Ind Microbiol Biotechnol 41, 1451–1456 (2014). https://doi.org/10.1007/s10295-014-1488-2

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  • DOI: https://doi.org/10.1007/s10295-014-1488-2

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