Initial Characterization of the Viridisins’ Biological Properties

• Published in: ACS omega Vol. 9; no. 29; pp. 31832 - 31841
• Main Authors: Vermeulen, Ross Rayne, van Staden, Anton Du Preez, Ollewagen, Tracey, van Zyl, Leonardo Joaquim, Luo, Youran, van der Donk, Wilfred A., Dicks, Leon Milner Theodore, Smith, Carine, Trindade, Marla
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 23.07.2024
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.4c03149

Viridisin A1 and A2 were previously heterologously expressed, purified, and characterized as ribosomally produced and post-translationally modified lanthipeptides. Such lanthipeptide operons are surprisingly common in Gram-negative bacteria, although their expression seems to be predominantly cryptic under laboratory conditions. However, the bioactivity and biological role of most lanthipeptide operons originating from marine-associated Pseudomonadota, such asThalassomonas viridans XOM25T, have not been described. Therefore, marine-associated Gram-negative lanthipeptide operons represent an untapped resource for novel structures, biochemistries, and bioactivities. Here, the upscaled production of viridisin A1 and A2 was performed for (methyl)­lanthionine stereochemistry characterization, antibacterial, antifungal, and larval zebrafish behavioral screening. While antimicrobial activity was not observed, the VirBC modification machinery was found to install both dl- and ll-lanthionine stereoisomers. The VdsA1 and VdsA2 peptides induced sedative and stimulatory effects in zebrafish larvae, respectively, which is a bioactivity not previously reported from lanthipeptides. When combined, VdsA1 and VdsA2 counteracted the sedative and stimulatory effects observed when used individually.