TY - JOUR TI - Post-translational flavinylation is associated with diverse extracytosolic redox functionalities throughout bacterial life AU - Méheust, Raphaël AU - Huang, Shuo AU - Rivera-Lugo, Rafael AU - Banfield, Jillian F AU - Light, Samuel H A2 - Cole, Philip A A2 - Chaiyen, Pimchai A2 - Chaiyen, Pimchai A2 - van Berkel, Willem A2 - Macheroux, Peter VL - 10 PY - 2021 DA - 2021/05/25 SP - e66878 C1 - eLife 2021;10:e66878 DO - 10.7554/eLife.66878 UR - https://doi.org/10.7554/eLife.66878 AB - Disparate redox activities that take place beyond the bounds of the prokaryotic cell cytosol must connect to membrane or cytosolic electron pools. Proteins post-translationally flavinylated by the enzyme ApbE mediate electron transfer in several characterized extracytosolic redox systems but the breadth of functions of this modification remains unknown. Here, we present a comprehensive bioinformatic analysis of 31,910 prokaryotic genomes that provides evidence of extracytosolic ApbEs within ~50% of bacteria and the involvement of flavinylation in numerous uncharacterized biochemical processes. By mining flavinylation-associated gene clusters, we identify five protein classes responsible for transmembrane electron transfer and two domains of unknown function (DUF2271 and DUF3570) that are flavinylated by ApbE. We observe flavinylation/iron transporter gene colocalization patterns that implicate functions in iron reduction and assimilation. We find associations with characterized and uncharacterized respiratory oxidoreductases that highlight roles of flavinylation in respiratory electron transport chains. Finally, we identify interspecies gene cluster variability consistent with flavinylation/cytochrome functional redundancies and discover a class of ‘multi-flavinylated proteins’ that may resemble multi-heme cytochromes in facilitating longer distance electron transfer. These findings provide mechanistic insight into an important facet of bacterial physiology and establish flavinylation as a functionally diverse mediator of extracytosolic electron transfer. KW - redox biochemistry KW - cellular respiration KW - extracellular microbial physiology JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -