Selective human trypsin inhibitors from cyanobacteria

Area of Science:

• Bioprospecting
• Natural Product Chemistry
• Enzyme Inhibition

Background:

• Aberrant human trypsin isoenzyme activity is linked to diseases such as cancer.
• Selective inhibition of human trypsin isoenzymes is challenging due to their high structural and catalytic similarity.
• Cyanobacteria are a rich source of diverse serine protease inhibitors with pharmaceutical potential.

Purpose of the Study:

• To investigate cyanobacteria as producers of selective inhibitors against human trypsin isoenzymes.
• To identify cyanobacterial strains and metabolites with selective inhibitory activity against human trypsin isoenzymes.

Main Methods:

• Screening of 505 aqueous cyanobacterial extracts from the Baltic Sea and Finnish lakes for inhibitory activity against human trypsin isoenzymes.
• Evaluation of selective extracts against plasma-kallikrein (KLK), bovine trypsin, Factor Xa, and thrombin.
• Molecular networking using high-resolution mass spectrometry to identify known and novel metabolites.

Main Results:

• 19% of tested cyanobacterial strains (98/505) exhibited inhibitory activity against one or more human trypsin isoenzymes.
• Specific extracts showed preferential inhibition of trypsin-1/trypsin-2 (24 strains), trypsin-2/trypsin-3 (8 strains), or trypsin-2 alone (7 strains).
• Molecular networking revealed both known and potentially novel metabolites, indicating diverse inhibitory compounds.

Conclusions:

• Cyanobacteria harbor a rich diversity of metabolites with selective inhibitory activity against human trypsin isoenzymes.
• These findings suggest cyanobacteria as a valuable resource for developing novel protease inhibitors.
• The identified compounds could serve as a starting point for therapeutic drug development targeting trypsin-related diseases.