BioNTech Investor Day Presentation Deck
Diverse and modular domain architecture allows flexibility in engineering
Enzymatically
active domain
EADS hydrolyze peptidoglycan
Different classes of EAD cleave 5 different
chemical bonds in peptidoglycan
There are 28++ classes of EADs
with low sequence similarity
Endolysins can have ≥1 EADs
Alphafold
homology model
of PM-477
Cell-wall
binding domain
CBDs bind specific features
on bacterial cell wall
CBDS mediate genus or species specificity
(but EADs also contribute to specificity)
15+ different classes of CBDs known
Outer-membrane
penetrating peptide (OMP)
Engineered endolysins can combine modules of multiple classes
High sequence diversity and option space, even within one class
CBD, Cell-wall binding domain; EAD, enzymatically active domain.
1 Oliveira H, et al. J Virol 2013; 87:4558-4570; 2 Vázquez R, et al. J Virol 2021; 95:e0032121; 3 Gutiérrez D & Briers Y. Curr Opin Biotechnol 2021; 68:15-22.
Enzymatically
active domain
To be active on Gram negative bacteria
(outer-cell membrane), many but not all
endolysins require outer-membrane
penetrating peptides
Antibacterials
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