Seven Cyclization Patterns of Type II PKS Yield Fluorescent Compounds, Including Fungal-Type Folded Globismycin A.

Area of Science:

• Natural Product Chemistry
• Biochemistry
• Synthetic Biology

Background:

• Aromatic polyketides are valuable fluorescent natural products for research and diagnostics.
• Understanding their biosynthesis is key to discovering new compounds and applications.

Purpose of the Study:

• To discover and characterize new fluorescent aromatic polyketides.
• To elucidate the biosynthetic pathways of these compounds.
• To explore the potential applications of novel fluorescent molecules.

Main Methods:

• Isolation and structural elucidation of new compounds.
• Spectroscopic analysis of fluorescence properties.
• Gene inactivation, heterologous expression, and isotopic labeling studies for biosynthesis.
• Cytotoxicity assays against cancer cell lines.

Main Results:

• Discovery of three new and ten known fluorescent aromatic polyketides with diverse spectral properties.
• Globismycin A (5) possesses a unique scaffold, high quantum yields, and selective cytotoxicity against cancer cells.
• All compounds originate from the type II polyketide synthase (PKS) gene cluster 'sgl', generated via seven distinct cyclization patterns.
• Globismycin A (5) exhibits an unusual cyclization step, despite its bacterial origin.

Conclusions:

• The study provides novel fluorescent compounds with potential applications in biological research and diagnostics.
• It expands the understanding of aromatic polyketide biosynthesis by type II PKS gene clusters.
• Globismycin A represents a significant discovery due to its unique structure, fluorescence, and bioactivity.