The study identifies a LD-transpeptidase from Gluconobacter oxydans, LDTGo, capable of generating 1,3 cross-links in the peptidoglycan. A high-resolution structure has been determined, revealing distinctive features.

The bacterial cell-wall peptidoglycan is made of glycan strands cross-linked by short peptide stems. Two different cross-link types have been long known, 4,3 and 3,3 cross-links, catalyzed by PBP transpeptidases and LD transpeptidases respectively. A multidimensional work led by Felipe Cava from Umeå University (Sweden), in collaboration with Juan A. Hermoso from the Institute of Physical Chemistry “Blas Cabrera” has explored novel cross-link types found in Alpha- and Betaproteobacteria, adding a new dimension to our understanding of bacterial cell-wall architecture. The study, published in Nature Communications, identifies a LD-transpeptidase from Gluconobacter oxydans, LDTGo, capable of generating 1,3 cross-links. LDTGo-like proteins have also been found among Alpha- and Betaproteobacteria, that lacks LD 3,3 transpeptidases. A high-resolution structure of LDTGo has been determined, revealing distinctive features including a Proline-rich region that limits substrate access, and a cavity for accommodating both glycan and peptide stem and responsible for the substrate specificity. These unique properties highlight the diversity of LD transpeptidases. Furthermore, the study demonstrates the dependence of 1,3 cross-link formation on substrate availability, involving the function of a DD endopeptidase. This discovery opens new avenues for understanding cell-wall integrity and maintenance in bacteria, particularly among Alpha and Betaproteobacteria.