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Discovery of novel septacidin congeners from a high yield heterologous expression strain Streptomyces albus 1597

The Journal of Antibiotics volume 75, pages 172–175 (2022)Cite this article

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Abstract

Septacidin is an adenine nucleoside antibiotic with antifungal and antitumor activities. During the efforts to construct a better septacidin producer, we obtained a high yield strain S. albus 1597 by putting the biosynthetic gene cluster (BGC) of septacidin under the control of the constitutive strong promoter ermE*. S. albus 1597 could produce new septacidin congeners SEP-538 and SEP-552 with shorter fatty acyl chains. Moreover, SEP-624 with an unprecedented hydroxylated fatty acyl chain was also isolated from this titre improved strain, enriching the diversity of septacidins. SEP-552 showed moderate inhibitory effects against Epidermophyton floccosum 57312 with MIC value 62.5 μM, while SEP-538 and SEP-624 only exhibited weak antifungal activities. The structure-activity relationship investigation revealed that the antifungal activity of septacidins is significantly influenced by the length of and the decoration on their fatty acyl chains.

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Acknowledgements

We thank Dr. Jinwei Ren and Dr. Wenzhao Wang, Institute of Microbiology, Chinese Academy of Sciences (CAS), for technical supports.

Funding

The study was financially supported by the MOST of China (2020YFA0907703) and the NSFC (31870043, 32025002). ZG is an awardee for “the Youth Innovation Promotion Association” of CAS (2017124).

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Author notes

  1. These authors contributed equally: Meng Chen, Zhenju Cao

Authors and Affiliations

  1. State Key Laboratory of Microbial Resources and CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China

    Meng Chen, Wei Tang, Min Wang, Yihua Chen & Zhengyan Guo

  2. University of Chinese Academy of Sciences, 100049, Beijing, China

    Meng Chen, Wei Tang, Min Wang, Yihua Chen & Zhengyan Guo

  3. Guizhou Institute of Biotechnology, Guizhou Academy of Agricultural Sciences, Guiyang, 550003, China

    Zhenju Cao

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  1. Meng Chen
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Correspondence to Yihua Chen or Zhengyan Guo.

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Chen, M., Cao, Z., Tang, W. et al. Discovery of novel septacidin congeners from a high yield heterologous expression strain Streptomyces albus 1597. J Antibiot 75, 172–175 (2022). https://doi.org/10.1038/s41429-022-00499-6

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