# Enzymatic activities of proteins encoded by PmurB, PmurC, and PmurE involved in methanogen pseudomurein biosynthesis

## TL;DR

This study identifies and characterizes enzymes involved in the biosynthesis of pseudomurein, a cell wall component in methanogens, revealing their enzymatic activities and structural similarities to bacterial enzymes.

## Contribution

The paper reports the enzymatic functions of PMurB, PMurC, and PMurE in pseudomurein biosynthesis and their structural comparison to bacterial Mur ligases.

## Key findings

- PMurB catalyzes the conjugation of UDP-Glu and Pi to form UDP.
- PMurC transfers alanine or threonine to UDP-Glu, and PMurE adds lysine to the product.
- Archaeal PMur enzymes share structural similarities with bacterial Mur ligases but differ in substrate specificity.

## Abstract

Pseudomurein, a glycan polymer present in the cell wall, is found in the orders Methanobacteriales and Methanopyrales. It possesses glycan units and peptide chains similar to those of bacterial peptidoglycan (murein). However, the biosynthesis of pseudomurein remains unknown. In this study, we identified and characterized several key enzymes, such as PMurBCE ligases, that are proposed to catalyse peptide chain biosynthesis. Specifically, PMurB catalyses the conjugation of UDP-Glu and Pi, forming UDP. PMurC then transfers alanine or threonine to UDP-Glu, and PMurE adds lysine to the PMurC product. These reactions represent the enzymatic activities of PMurBCE ligases in methanogens. Structural model analyses indicated that archaeal PMur enzymes share an overall structural arrangement similar to that of bacterial Mur ligases but exhibit specificity for different substrates. The structural model data provide insights into pseudomurein synthesis in methanogens and create promising avenues for biotechnological applications in methanogens, such as gene editing and the development of novel antibacterial agents targeting methanogenic archaea.