Bioinformatic Analysis of Lytic Polysaccharide Monooxygenases Reveals the Pan-Families Occurrence of Intrinsically Disordered C-Terminal Extensions

Lytic polysaccharide monooxygenases (LPMOs) are monocopper enzymes secreted by many organisms and viruses. LPMOs catalyze the oxidative cleavage of different types of polysaccharides and are today divided into eight families (AA9-11, AA13-17) within the Auxiliary Activity enzyme class of the CAZy database. LPMOs minimal architecture encompasses a catalytic domain, to which can be appended a carbohydrate-binding module. Intriguingly, we observed that some LPMO sequences also display a C-terminal extension of varying length not associated with any known function or fold. Here, we analyzed 27,060 sequences from different LPMO families and show that 60% have a C-terminal extension predicted to be intrinsically disordered. Our analysis shows that these disordered C-terminal regions (dCTRs) are widespread in all LPMO families (except AA13) and differ in terms of sequence length and amino-acid composition. Noteworthily, these dCTRs have so far only been observed in LPMOs. LPMO-dCTRs share a common polyampholytic nature and an enrichment in serine and threonine residues, suggesting that they undergo post-translational modifications. Interestingly, dCTRs from AA11 and AA15 are enriched in redox-sensitive, conditionally disordered regions. The widespread occurrence of dCTRs in LPMOs from evolutionarily very divergent organisms, hints at a possible functional role and opens new prospects in the field of LPMOs.

Automated summary

Lytic polysaccharide monooxygenases (LPMOs) are monocopper enzymes that catalyze the oxidative cleavage of polysaccharides. A study analyzing 27,060 LPMO sequences found that 60% of them have a predicted intrinsically disordered C-terminal extension, indicating a common polyampholytic nature and potential for post-translational modifications. This widespread occurrence of disordered C-terminal regions in LPMOs suggests a possible functional role and opens up new prospects in this field.