Fibrotisiin

Fibrotisiin is a secondary metabolite produced by certain filamentous fungi. It is described as a small-molecule natural product featuring a macrocyclic core with multiple oxygen-containing substituents and a planar polycyclic ring system. The compound has been reported from culture filtrates of fungi isolated from soil environments, and is typically obtained as a pale-yellow crystalline solid after chromatographic purification.

Isolation and structure elucidation rely on standard natural product techniques, including solvent extraction, high-performance liquid chromatography, nuclear magnetic resonance spectroscopy, and mass spectrometry. While several research groups have reported slightly different substituent patterns, the core macrocycle and hydroxy-containing side chains are generally consistent across isolates. The exact stereochemistry has been a focus of ongoing structural work.

Biosynthesis is attributed to a fungal polyketide synthase (PKS)–based pathway, with tailoring enzymes introducing hydroxylations, methylations, and possible glycosylation. The gene cluster is thought to encode a multi-domain PKS along with ancillary oxidoreductases and cyclases that construct the macrocycle.

Biological activity studies show fibrotisiin exhibits in vitro antifungal activity against several plant and clinical pathogens and displays limited antibacterial effects in some assays. It also shows cytotoxic activity in certain cancer cell lines at micromolar concentrations, though selectivity toward mammalian cells remains a concern. The mechanism of action has not been conclusively established; proposed effects include disruption of membrane integrity or interference with nucleic acid processes, but further work is needed.

At present, fibrotisiin is not approved for medical use. Research is focused on clarifying its structure–activity relationships, improving solubility and stability, and assessing in vivo toxicity and pharmacokinetics. As a scaffold for drug discovery, it remains a subject of interest for antifungal and anticancer lead development.