The team’s work is a response to a very general problem: the widening gap between the discovery of proteins by new sequencing technologies (which is growing exponentially), and the discovery of their functions, which remains very slow. This complexity is reduced by grouping proteins into families in which functions are assigned based on the annotation of some of their members. However, the function of certain families remains mysterious. Yet, they represent a significant source of new functions and deserve special interest.

To better understand these families, the researchers used contextual and structural information coupled with experimental analyses. Previous work on the fermentation of lysine [1] guided their choice towards a protein family of unknown function (DUF849).
The team first identified the function of one of its members and determined its reaction mechanism by analysis of its three-dimensional structure. The approach developed is based on an experimental high-throughput screening, performed on representatives carefully selected by modeling of their 3D structures and the study of their genetic environment. Applied to DUF849, this method resulted in the discovery of a large number of activities, some of which are linked to a metabolic context. This also enabled annotating the function of members of the family on the basis of structural motifs.

Extending this analysis to other families should allow access to the hidden part of bacterial metabolism.

[1] One of the amino acids making up proteins.