School of Podiatric Medicine Publications and Presentations
Document Type
Article
Publication Date
12-10-2024
Abstract
Bacterial membranes are complex and dynamic, arising from an array of evolutionary pressures. One enzyme that alters membrane compositions through covalent lipid modification is MprF. We recently identified that Streptococcus agalactiae MprF synthesizes lysyl-phosphatidylglycerol (Lys-PG) from anionic PG, and a novel cationic lipid, lysyl-glucosyldiacylglycerol (Lys-Glc-DAG), from neutral glycolipid Glc-DAG. This unexpected result prompted us to investigate whether Lys-Glc-DAG occurs in other MprF-containing bacteria, and whether other novel MprF products exist. Here, we studied protein sequence features determining MprF substrate specificity. First, pairwise analyses identified several streptococcal MprFs synthesizing LysGlc-DAG. Second, a restricted Boltzmann machine-guided approach led us to discover an entirely new substrate for MprF in Enterococcus, diglucosyl-diacylglycerol (Glc2-DAG), and an expanded set of organisms that modify glycolipid substrates using MprF. Overall, we combined the wealth of available sequence data with machine learning to model evolutionary constraints on MprF sequences across the bacterial domain, thereby identifying a novel cationic lipid.
Recommended Citation
Christensen, P. M., Martin, J., Uppuluri, A., Joyce, L. R., Wei, Y., Guan, Z., ... & Palmer, K. L. (2024). Lipid discovery enabled by sequence statistics and machine learning. Elife, 13, RP94929. https://doi.org/10.7554/eLife.94929
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
eLife
Figures and Suplements
Academic Level
faculty
DOI
10.7554/eLife.94929
Comments
Copyright Christensen, Martin et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.