Post-translational flavinylation is associated with diverse extracytosolic redox functionalities throughout bacterial life

  1. Raphaël Méheust
  2. Shuo Huang
  3. Rafael Rivera-Lugo
  4. Jillian F Banfield
  5. Samuel H Light  Is a corresponding author
  1. University of California, Berkeley, United States
  2. The University of Chicago, United States

Abstract

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 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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following previously published data sets were used

Article and author information

Author details

  1. Raphaël Méheust

    Innovative Genomics Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4847-426X
  2. Shuo Huang

    Microbiology, The University of Chicago, Chicago, United States
    Competing interests
    No competing interests declared.
  3. Rafael Rivera-Lugo

    Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2346-2297
  4. Jillian F Banfield

    Department of Earth and Planetary Science, University of California, Berkeley, Berkeley, United States
    Competing interests
    Jillian F Banfield, is a founder of Metagenomi.
  5. Samuel H Light

    Microbiology, The University of Chicago, Chicago, United States
    For correspondence
    samlight@uchicago.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8074-1348

Funding

National Institute of Allergy and Infectious Diseases (K22 AI144031)

  • Samuel H Light

Ford Foundation

  • Rafael Rivera-Lugo

Chan Zuckerberg Initiative

  • Raphaël Méheust
  • Jillian F Banfield

Innovative Genomics Institute

  • Raphaël Méheust
  • Jillian F Banfield

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Pimchai Chaiyen, Vidyasirimedhi Institute of Science and Technology (VISTEC), Thailand

Publication history

  1. Received: January 25, 2021
  2. Accepted: May 24, 2021
  3. Accepted Manuscript published: May 25, 2021 (version 1)
  4. Version of Record published: June 28, 2021 (version 2)

Copyright

© 2021, Méheust et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Raphaël Méheust
  2. Shuo Huang
  3. Rafael Rivera-Lugo
  4. Jillian F Banfield
  5. Samuel H Light
(2021)
Post-translational flavinylation is associated with diverse extracytosolic redox functionalities throughout bacterial life
eLife 10:e66878.
https://doi.org/10.7554/eLife.66878
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