Initial Characterization of the Viridisins' Biological Properties

Area of Science:

• Microbiology
• Biochemistry
• Marine Biology

Background:

• Lanthipeptide operons are common in Gram-negative bacteria but often cryptic.
• Marine-associated *Pseudomonadota* represent a source of novel lanthipeptides.
• The bioactivity of most marine lanthipeptide operons remains undescribed.

Purpose of the Study:

• Investigate the bioactivity of viridisin A1 and A2 from *Thalassomonas viridans*.
• Characterize the stereochemistry of (methyl)lanthionine residues.
• Screen for antibacterial, antifungal, and zebrafish behavioral effects.

Main Methods:

• Upscaled production of viridisin A1 and A2.
• Stereochemical analysis of (methyl)lanthionine.
• Antibacterial, antifungal, and larval zebrafish behavioral assays.

Main Results:

• Viridisin A1 and A2 exhibited no antimicrobial activity.
• The VirBC modification machinery produced both dl- and ll-lanthionine stereoisomers.
• VdsA1 and VdsA2 peptides induced sedative and stimulatory effects in zebrafish larvae, respectively, with combined effects neutralizing individual impacts.

Conclusions:

• Marine lanthipeptide operons are a source of novel bioactivities beyond antimicrobial effects.
• The VirBC machinery can install diverse lanthionine stereoisomers.
• Viridisin peptides modulate zebrafish behavior, highlighting a new class of lanthipeptide function.