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Titer improvement and pilot-scale production of platensimycin from Streptomyces platensis SB12026

  • Natural Products
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Platensimycin (PTM) and platencin (PTN), isolated from several strains of Streptomyces platensis are potent antibiotics against multi-drug resistant bacteria. PTM was also shown to have antidiabetic and antisteatotic activities in mouse models. Through a novel genome-mining method, we have recently identified six PTM and PTN dual-producing strains, and generated several mutants with improved production of PTM or PTN by inactivating the pathway-specific transcriptional repressor gene ptmR1. Among them, S. platensis SB12026 gave the highest titer of 310 mg/L for PTM. In this study, we now report titer improvement by medium and fermentation optimization and pilot-scale production and isolation of PTM from SB12026. The fermentation medium optimization was achieved by manipulating the carbon and nitrogen sources, as well as the inorganic salts. The highest titer of 1560 mg/L PTM was obtained in 15-L fermentors, using a formulated medium mainly containing soluble starch, soybean flour, morpholinepropanesulfonic acid sodium salt and CaCO3. In addition, a polyamide chromatographic step was applied to facilitate the purification and 45.14 g of PTM was successfully obtained from a 60 L scale fermentation. These results would speed up the future development of PTM as human medicine.

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Acknowledgments

This work is supported in part by a startup fund from Central South University (CSU) 165000001 (to Y.D. and Y.H.), the Chinese Ministry of Education 111 Project B0803420 (to Y.D.), National High Technology Joint Research Program of China Grant 2011ZX09401-001 (to Y.D.), and US National Institutes of Health Grants GM 114353 (to B.S.). We are grateful to Dr. Lin Qiu and the Center for Advanced Research in CSU in assisting to acquire the 1H NMR of platensimycin.

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Authors and Affiliations

  1. Xiangya International Academy of Translational Medicine, Central South University, Tongzipo Road, #172, Yuelu District, Changsha, 410013, Hunan, China

    Jun Shi, Jian Pan, Ling Liu, Xiangcheng Zhu, Yanwen Duan & Yong Huang

  2. Hunan Engineering Research Center of Combinatorial Biosynthesis and Natural Product Drug Discovery, Changsha, 410013, Hunan, China

    Songquan Lu, Xiangcheng Zhu & Yanwen Duan

  3. National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery, Changsha, 410013, Hunan, China

    Yanwen Duan & Yong Huang

  4. Department of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA

    Dong Yang & Ben Shen

  5. Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, 33458, USA

    Ben Shen

  6. Natural Products Library Initiative, The Scripps Research Institute, Jupiter, FL, 33458, USA

    Ben Shen

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  1. Jun Shi
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  2. Jian Pan
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  3. Ling Liu
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Correspondence to Yanwen Duan or Yong Huang.

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Shi, J., Pan, J., Liu, L. et al. Titer improvement and pilot-scale production of platensimycin from Streptomyces platensis SB12026. J Ind Microbiol Biotechnol 43, 1027–1035 (2016). https://doi.org/10.1007/s10295-016-1769-z

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