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Production of pikromycin using branched chain amino acid catabolism in Streptomyces venezuelae ATCC 15439

  • Fermentation, Cell Culture and Bioengineering - Original Paper
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Branched chain amino acids (BCAA) are catabolized into various acyl-CoA compounds, which are key precursors used in polyketide productions. Because of that, BCAA catabolism needs fine tuning of flux balances for enhancing the production of polyketide antibiotics. To enhance BCAA catabolism for pikromycin production in Streptomyces venezuelae ATCC 15439, three key enzymes of BCAA catabolism, 3-ketoacyl acyl carrier protein synthase III, acyl-CoA dehydrogenase, and branched chain α-keto acid dehydrogenase (BCDH) were manipulated. BCDH overexpression in the wild type strain resulted in 1.3 fold increase in pikromycin production compared to that of WT, resulting in total 25 mg/L of pikromycin. To further increase pikromycin production, methylmalonyl-CoA mutase linked to succinyl-CoA production was overexpressed along with BCDH. Overexpression of the two enzymes resulted in the highest titer of total macrolide production of 43 mg/L, which was about 2.2 fold increase compared to that of the WT. However, it accumulated and produced dehydroxylated forms of pikromycin and methymycin, including their derivatives as well. It indicated that activities of pikC, P450 monooxygenase, newly became a bottleneck in pikromycin synthesis.

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Acknowledgements

This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2016953757). The Institute of Engineering Research at Seoul National University provided research facilities for this work.

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Authors and Affiliations

  1. School of Chemical and Biological Engineering, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea

    Jeong Sang Yi & Byung-Gee Kim

  2. Institute of Molecular Biology and Genetics, Seoul National University, Seoul, 08826, Republic of Korea

    Jeong Sang Yi, Eun-Jung Kim & Byung-Gee Kim

  3. Institute of Engineering Research, Seoul National University, Seoul, 08826, Republic of Korea

    Minsuk Kim & Byung-Gee Kim

  4. Interdisciplinary Program for Biochemical Engineering and Biotechnology, and Bioengineering Institute, Seoul National University, Seoul, 08826, Republic of Korea

    Byung-Gee Kim

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  1. Jeong Sang Yi
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Correspondence to Byung-Gee Kim.

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Yi, J.S., Kim, M., Kim, EJ. et al. Production of pikromycin using branched chain amino acid catabolism in Streptomyces venezuelae ATCC 15439. J Ind Microbiol Biotechnol 45, 293–303 (2018). https://doi.org/10.1007/s10295-018-2024-6

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  • DOI: https://doi.org/10.1007/s10295-018-2024-6

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