000009892 001__ 9892
000009892 005__ 20250218124639.0
000009892 02470 $$ahttps://doi.org/10.7554/eLife.66878$$2doi
000009892 037__ $$aTEXTUAL
000009892 041__ $$aeng
000009892 245__ $$aPost-translational flavinylation is associated with diverse extracytosolic redox functionalities throughout bacterial life
000009892 269__ $$a2021-05-25
000009892 336__ $$aArticle
000009892 520__ $$aDisparate 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 multiheme cytochromes in facilitating longer distance electron transfer. These findings provide key mechanistic insight into an important facet of bacterial physiology and establish flavinylation as a functionally diverse mediator of extracytosolic electron transfer. 
000009892 536__ $$oNational Institute of Allergy and Infectious Diseases$$cK22 AI144031
000009892 536__ $$oFord Foundation
000009892 536__ $$oChan Zuckerberg Initiative
000009892 536__ $$oInnovative Genomics Institute
000009892 540__ $$a&lt;p&gt; © 2021, Méheust et al.&lt;/p&gt; &lt;p&gt;This article is distributed under the terms of the &lt;a href="http://creativecommons.org/licenses/by/4.0/" target="_blank"&gt;Creative Commons Attribution License&lt;/a&gt;, which permits unrestricted use and redistribution provided that the original author and source are credited.&lt;/p&gt;
000009892 542__ $$fCC BY
000009892 594__ $$a&lt;p&gt;All data generated or analysed during this study are included in the manuscript and supporting files.&lt;/p&gt;
&lt;p&gt;The following previously published data sets were used:&lt;/p&gt;
&lt;p&gt;Parks D Chuvochina Waite Rinke Skarshewski Chaumeil Hugenholtz (2019) NCBI/GTDB ID 30148503. A standardized bacterial taxonomy based on genome phylogeny substantially revises the tree of life (release R04-RS89). &lt;a href="https://data.gtdb.ecogenomic.org/releases/release89/"&gt;https://data.gtdb.ecogenomic.org/releases/release89/&lt;/a&gt;&lt;/p&gt;
000009892 6531_ $$aredox biochemistry
000009892 6531_ $$acellular respiration
000009892 6531_ $$aextracellular microbial physiology
000009892 690__ $$aBiological Sciences Division
000009892 691__ $$aMicrobiology
000009892 692__ $$aDuchossois Family Institute
000009892 7001_ $$1https://orcid.org/0000-0002-4847-426X$$2ORCID$$aMéheust, Raphaël$$uUniversity of California, Berkeley
000009892 7001_ $$aHuang, Shuo$$uUniversity of Chicago
000009892 7001_ $$1https://orcid.org/0000-0002-2346-2297$$2ORCID$$aRivera-Lugo, Rafael$$uUniversity of California, Berkeley
000009892 7001_ $$aBanfield, Jillian F.$$uUniversity of California, Berkeley
000009892 7001_ $$1https://orcid.org/0000-0002-8074-1348$$2ORCID$$aLight, Samuel H.$$uUniversity of Chicago
000009892 773__ $$teLife
000009892 8564_ $$yArticle$$9c9a5ddaf-6493-4efd-be77-993d9e0b567c$$s6385630$$uhttps://knowledge.uchicago.edu/record/9892/files/elife-66878-v2.pdf$$ePublic
000009892 8564_ $$yAdditional files$$918460e8f-8beb-4a3c-b0f0-c11b196fa8a4$$s22221404$$uhttps://knowledge.uchicago.edu/record/9892/files/elife-66878.zip$$ePublic
000009892 908__ $$aI agree
000009892 909CO $$ooai:uchicago.tind.io:9892$$pGLOBAL_SET
000009892 983__ $$aArticle