# Hidden Activities of Tyrosine Phenol-Lyase and Tryptophan Indole-Lyase: Recombinant PLP-Dependent C–C Lyases as New Biocatalysts for Antimicrobial Thiosulfinate Generation

## TL;DR

This paper discovers new enzyme activities that can produce antimicrobial compounds from specific amino acid derivatives.

## Contribution

First demonstration that C–C lyases can act as C–S lyases to synthesize thiosulfinates from cysteine sulfoxides.

## Key findings

- TPL and Trpase, along with MGL, can degrade petiveriin into thiosulfinates.
- Enzyme-generated thiosulfinates show antimicrobial activity against pathogens like Candida albicans and Staphylococcus aureus.

## Abstract

Background: Lyases are used in a wide scope of applications, making them invaluable tools in both industrial biotechnology and molecular biology. Many examples of lyases belong to the extensive family of pyridoxal 5′-phosphate (PLP)-dependent enzymes, which catalyze numerous reactions involved in amino acid metabolism, like tryptophan indole-lyase (Trpase or Tnase), tyrosine phenol-lyase (TPL), and methionine γ-lyase (MGL). Beyond their role in physiological processes, these lyases can also facilitate the synthesis of other biologically active products from non-canonical substrates. Objectives: Up till now there were only two C–S lyases known for the thiosulfinates’ biosynthesis from S-substituted L-cysteine sulfoxides—alliinase and MGL. Our study reveals for the first time that C–C lyases are capable of C–S lyase activity in reactions with S-alkyl, S-allyl and S-benzyl cysteine sulfoxides. Methods: We have compared the kinetic profiles of S-substituted L-cysteine sulfoxide degradation mediated by carbon–sulfur lyase MGL versus carbon–carbon lyases TPL and Trpase. Results: Among other S-alkyl-L-cysteine sulfoxides, petiveriin (S-benzyl-L-cysteine sulfoxide) was proven to be a substrate for all three enzymes. The potential utility of these enzymes in thiosulfinate production was supported by in vitro testing of enzyme-generated thiosulfinates against clinically relevant pathogens such as Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus. Conclusions: Both C–S and C–C lyases—MGL, TPL, and Trpase—can be implemented for practical application in thiosulfinate synthesis.