[Exploiting bioactive Enediynes from marine microbe based on activity and gene screening]

Area of Science:

• Marine microbiology
• Natural product chemistry
• Drug discovery

Context:

• A high-quality marine microbial natural product library is essential for identifying novel drug candidates.
• Enediyne compounds are a promising class of natural products with potent biological activities.
• Assessing library quality is critical for efficient drug discovery pipelines.

Purpose:

• To establish a method for assessing the quality of a marine microbial natural product library.
• To screen for novel enediyne-like compounds within the library.
• To validate both activity-based and sequence-based screening approaches for enediyne discovery.

Summary:

• Developed and applied a high-throughput, DNA-damage activity-based screening assay to identify enediyne-like compounds.
• Utilized a sequence-based screening method targeting conserved polyketide synthase genes for enediyne biosynthesis.
• Activity-based screening yielded a positive hit (LS481), closely related to Dynemicin-producing Micromonospora.
• Sequence-based screening identified two strains (MS098, LS2004) with high similarity to known Streptomyces species.

Impact:

• Successfully isolated enediyne compounds through activity-based screening.
• Demonstrated the utility of sequence-based screening for predicting enediyne production potential.
• Enhanced the quality assessment of marine microbial libraries for drug discovery.
• Provided a foundation for further exploration of marine natural products.