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Conversion of the high-yield salinomycin producer Streptomyces albus BK3-25 into a surrogate host for polyketide production

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Abstract

An ideal surrogate host for heterologous production of various natural products is expected to have efficient nutrient utilization, fast growth, abundant precursors and energy supply, and a pronounced gene expression. Streptomyces albus BK3-25 is a high-yield industrial strain producing type-I polyketide salinomycin, with a unique ability of bean oil utilization. Its potential of being a surrogate host for heterologous production of PKS was engineered and evaluated herein. Firstly, introduction of a three-gene cassette for the biosynthesis of ethylmalonyl-CoA resulted in accumulation of ethylmalonyl-CoA precursor and salinomycin, and subsequent deletion of the salinomycin biosynthetic gene cluster resulted in a host with rich supplies of common polyketide precursors, including malonyl-CoA, methylmalonyl-CoA, and ethylmalonyl-CoA. Secondly, the energy and reducing force were measured, and the improved accumulation of ATP and NADPH was observed in the mutant. Furthermore, the strength of a series of selected endogenous promoters based on microarray data was assessed at different growth phases, and a strong constitutive promoter was identified, providing a useful tool for further engineered gene expression. Finally, the potential of the BK3-25 derived host ZXJ-6 was evaluated with the introduction of the actinorhodin biosynthetic gene cluster from Streptomyces coelicolor, and the heterologous production of actinorhodin was obtained. This work clearly indicated the potential of the high-yield salinomycin producer as a surrogate host for heterologous production of polyketides, although more genetic manipulation should be conducted to streamline its performance.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (21661140002 and 31470157) and the Ministry of Science and Technology of China (2012CB721005 and 2012AA022107). We are grateful to Prof. Yongquan Li (Zhejiang University) and Zhejiang Shenghua Biok Biology Co., Ltd. for providing the strain S. albus BK3-25. We are grateful to Dr. Meifeng Tao (Shanghai Jiao Tong University) for providing the plasmid pMM1.

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Authors and Affiliations

  1. State Key Laboratory of Microbial Metabolism and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China

    Xiaojie Zhang, Chenyang Lu & Linquan Bai

  2. School of Marine Sciences, Ningbo University, Ningbo, 315211, China

    Chenyang Lu

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  1. Xiaojie Zhang
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  2. Chenyang Lu
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Correspondence to Linquan Bai.

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Zhang, X., Lu, C. & Bai, L. Conversion of the high-yield salinomycin producer Streptomyces albus BK3-25 into a surrogate host for polyketide production. Sci. China Life Sci. 60, 1000–1009 (2017). https://doi.org/10.1007/s11427-017-9122-8

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  • DOI: https://doi.org/10.1007/s11427-017-9122-8

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