2. Academic Validation
  3. Discovery of novel septacidin congeners from a high yield heterologous expression strain Streptomyces albus 1597

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

  • J Antibiot (Tokyo). 2022 Mar;75(3):172-175. doi: 10.1038/s41429-022-00499-6.
Meng Chen # 1 2,  Zhenju Cao # 3,  Wei Tang 1 2,  Min Wang 1 2,  Yihua Chen 4 5,  Zhengyan Guo 6 7
Affiliations

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.
  • 2 University of Chinese Academy of Sciences, 100049, Beijing, China.
  • 3 Guizhou Institute of Biotechnology, Guizhou Academy of Agricultural Sciences, Guiyang, 550003, China.
  • 4 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. [email protected].
  • 5 University of Chinese Academy of Sciences, 100049, Beijing, China. [email protected].
  • 6 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. [email protected].
  • 7 University of Chinese Academy of Sciences, 100049, Beijing, China. [email protected].
  • # Contributed equally.
PMID: 35082443 DOI: 10.1038/s41429-022-00499-6
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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