Light-Triggered Carotenogenesis in Myxococcus xanthus: New Paradigms in Photosensory Signaling, Transduction and Gene Regulation

Abstract

Myxobacteria are Gram-negative δ-proteobacteria found predominantly in terrestrial habitats and often brightly colored due to the biosynthesis of carotenoids. Carotenoids are lipophilic isoprenoid pigments that protect cells from damage and death by quenching highly reactive and toxic oxidative species, like singlet oxygen, generated upon growth under light. The model myxobacterium Myxococcus xanthus turns from yellow in the dark to red upon exposure to light because of the photoinduction of carotenoid biosynthesis. How light is sensed and transduced to bring about regulated carotenogenesis in order to combat photooxidative stress has been extensively investigated in M. xanthus using genetic, biochemical and high-resolution structural methods. These studies have unearthed new paradigms in bacterial light sensing, signal transduction and gene regulation, and have led to the discovery of prototypical members of widely distributed protein families with novel functions. Major advances have been made over the last decade in elucidating the molecular mechanisms underlying the light-dependent signaling and regulation of the transcriptional response leading to carotenogenesis in M. xanthus. This review aims to provide an up-to-date overview of these findings and their significance.

Coenzyme B12‐dependent and independent photoregulation of carotenogenesis across Myxococcales

“…Many organisms, including bacteria, combat photooxidative stress by inducing the synthesis of carotenoids, pigments that quench ROS (Armstrong, 1997 ; Ziegelhoffer and Donohue, 2009 ; Rodriguez‐Concepción et al ., 2018 ; Sandmann, 2019 ). How light is sensed and signalled to trigger carotenogenesis has been studied in depth in Myxococcus xanthus (Elías‐Arnanz et al ., 2011 ; Padmanabhan et al ., 2021 ), a Gram‐negative soil bacterium of the order Myxococcales, currently included within the class Deltaproteobacteria but it was recently proposed that this order be moved to a new and independent phylum with the name Myxococcata (Waite et al ., 2020 ). Members of this order, the myxobacteria, form an important group of ubiquitous, predominantly aerobic, soil bacteria that share complex lifestyles and several traits typical of eukaryotes, such as multicellular development, biosynthesis of specialized lipids and steroids, social behaviour, kin recognition (the ability of an individual cell or organism to identify others as self‐like), predation and motility (Muñoz‐Dorado et al ., 2016 ; Cao and Wall, 2019 ; Gallego‐García et al ., 2019 ; Hoshino and Gaucher, 2021 ).…”

Plasmalogens and Photooxidative Stress Signaling in Myxobacteria, and How it Unmasked CarF/TMEM189 as the Δ1′-Desaturase PEDS1 for Human Plasmalogen Biosynthesis

“…Myxobacteria are striking in their complex lifestyles, with some traits usually attributed to eukaryotes, like multicellular development, social cooperative behavior, kin recognition, predation, motility and, pertinent to this review, biosynthesis of specialized lipids and steroids ( Muñoz-Dorado et al, 2016 ; Cao and Wall, 2019 ; Gallego-García et al, 2019 ; Hoshino and Gaucher, 2021 ). These aspects have been investigated in Myxococcus xanthus that, as a model bacterial system to study light sensing and response, has uncovered new photosensory transduction and gene regulation paradigms ( Elías-Arnanz et al, 2011 ; Padmanabhan et al, 2021 ), including the aforementioned conserved desaturase for plasmalogen biosynthesis ( Gallego-García et al, 2019 ).…”

“…The surprising road to unmasking CarF in M. xanthus and its homologue TMEM189 in metazoa as the conserved Δ1′-desaturase for plasmalogen formation was paved in studies that examined how M. xanthus responds to light by synthesizing carotenoids, which quench 1 O 2 produced upon illumination and thereby protect cells against photooxidative damage ( Padmanabhan et al, 2021 ). Carotenoids are lipophilic isoprenoid pigments with extended, all-trans, conjugated polyene chains (usually C40, sometimes C50, C45 and C30 terpenes) with acyclic, monocyclic, or bicyclic ends.…”

“…Two modes of light sensing and signaling operate in M. xanthus to trigger a transcriptional response leading to carotenoid biosynthesis ( Padmanabhan et al, 2021 ; Pérez-Castaño et al, 2022 ). In one, the photoreceptor protein CarH, with coenzyme B 12 as its chromophore, directly senses UV, blue or green light and turns on transcription of genes encoding enzymes required for carotenogenesis ( Ortiz-Guerrero et al, 2011 ; Jost et al, 2015 ; Padmanabhan et al, 2017 ; Padmanabhan et al, 2019 ; Padmanabhan et al, 2022 ).…”

“… Phylogenetic distribution and conserved histidines of CarF homologues. (A) Phylogenetic tree for CarF homologues in metazoa, bacteria and plants (maximum-likelihood with red branches for ≥ 75% confidence from 200 bootstrap replicates; scale bar, number of substitutions per residue; key below for colored sectors; adapted from ( Padmanabhan et al, 2021 ). Homologues that were tested for CarF function in M. xanthus are indicated: Hs, Homo sapiens ; Mm, M. musculus ; Dr, D. rerio (two homologues); Dm, D. melanogaster ; Ce, C. elegans ; Mx, M. xanthus ; Li, Leptospira interrogans ; Bd, Bradyrhizobium diazoefficiens ; At, A. thaliana (three homologues).…”