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A Cyclodepsipeptide Nature Product from Saccharothrix Syringae Targets DNA in Its Mode of Action

  • Ke DU

Student thesis: Doctoral thesis

Abstract

Saccharothrix syringae (DSM 43886) is a renowned strain known for producing the natural product Nocamycin, which exhibits remarkable antibacterial properties[1]. In our research, we discovered a novel natural product SacA from Saccharothrix syringae fermentation, structurally distinct from previously reported compounds from the same strain. This new compound is a cyclodepsipeptide that targets DNA as its mode of action.

Our experiments involving various types of DNA revealed that this compound exclusively binds to double-stranded DNA. Additionally, we isolated the compound dissociated from the DNA through denaturing the cyclodepsipeptide-bound DNA by heating at 95℃. LC-MS analysis confirmed that the compound was a cyclic peptide, confirming the non-covalent interaction between the natural product and DNA. In vivo experiments have shown that SacA successfully induced the SOS response of Bacillus subtilis and confirmed that RecA is the responsible gene for this response. Unlike typical DNA-binding compounds such as mitomycin C, SacA does not cause the activation of spβ prophages in host cells, which is attributed to the inactivation of prophages. Surface plasmon resonance technology has revealed a strong and rapid binding between SacA and DNA. The new generation of sequencing technology further assisted in the analysis of the interaction between SacA and DNA, confirming its potential as a probe to explore the structure of DNA during metabolic processes.

Date of Award2026
Original languageEnglish
Awarding Institution
  • The Hong Kong University of Science and Technology
SupervisorZhihong GUO (Supervisor)

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