Uneven distribution of cobamide biosynthesis and dependence in bacteria predicted by comparative genomics

Abstract

The vitamin B 12 family of cofactors known as cobamides are essential for a variety of microbial metabolisms. We used comparative genomics of 11,000 bacterial species to analyze the extent and distribution of cobamide production and use across bacteria. We find that 86% of bacteria in this data set have at least one of 15 cobamide-dependent enzyme families, but only 37% are predicted to synthesize cobamides de novo. The distribution of cobamide biosynthesis and use vary at the phylum level. While 57% of Actinobacteria are predicted to biosynthesize cobamides, only 0.6% of Bacteroidetes have the complete pathway, yet 96% of species in this phylum have cobamide-dependent enzymes. The form of cobamide produced by the bacteria could be predicted for 58% of cobamide-producing species, based on the presence of signature lower ligand biosynthesis and attachment genes. Our predictions also revealed that 17% of bacteria have partial biosynthetic pathways, yet have the potential to salvage cobamide precursors. Bacteria with a partial cobamide biosynthesis pathway include those in a newly defined, experimentally verified category of bacteria lacking the first step in the biosynthesis pathway. These predictions highlight the importance of cobamide and cobamide precursor salvaging as examples of nutritional dependencies in bacteria.

Genome‐resolved viral and cellular metagenomes revealed potential key virus‐host interactions in a deep freshwater lake

“…LBVG_55, one of the dominant viruses in the hypolimnion with an unknown host (Fig. 5), encoded genes (cobS and cobT) involved in the biosynthesis of cobalamin, which is often absent from bacterial genomes, thus limiting their metabolic capability (Shelton et al, 2019). Several LBVGs harboured a cluster of genes involved in the biosynthesis of lipopolysaccharides (LPS) and capsular polysaccharides.…”

Genome-resolved viral and cellular metagenomes revealed potential key virus-host interactions in a deep freshwater lake

“…LBVG_55, one of the dominant viruses in the hypolimnion with an unknown host ( Fig. 5), encoded genes (cobS and cobT) involved in the biosynthesis of cobalamin, which is often absent from bacterial genomes, thus limiting their metabolic capability (Shelton et al, 2019). Several LBVGs harbored a cluster of genes involved in the biosynthesis of lipopolysaccharides (LPS) and capsular polysaccharides.…”

Cofactor selectivity in methylmalonyl-CoA mutase, a model cobamide-dependent enzyme

“…Bacteria and archaea additionally use cobalamin and related cofactors, cobamides, for deoxyribonucleotide synthesis [3], metabolism of various carbon and energy sources [4][5][6][7][8][9][10][11][12][13][14][15][16][17], synthesis of secondary metabolites [18][19][20][21][22][23][24][25], sensing light [26], and other processes [15][16][17][27][28][29][30][31][32]. The finding that 86% of bacterial species encode at least one cobamide-dependent enzyme in their genome [33] demonstrates the prevalence of cobamide-dependent metabolisms. Widespread use of these cofactors can be attributed to their chemical versatility, as they facilitate challenging chemical reactions including radical-initiated rearrangements, methylation reactions, and reductive cleavage of chemical bonds [34,35].…”

“…Bacteria and archaea additionally use cobalamin and related cofactors, cobamides, for deoxyribonucleotide synthesis (Licht et al, 1996), metabolism of various carbon and energy sources (Barker, 1985;Berg et al, 2007;Chang and Frey, 2000;Chen et al, 2001;Erb et al, 2008;Ferguson and Krzycki, 1997;Forage and Foster, 1982;Jeter, 1990;Korotkova et al, 2002;Krasotkina et al, 2001;Ljungdahl, 1986;Scarlett and Turner, 1976;Stupperich and Konle, 1993;Vrijbloed et al, 1999), synthesis of secondary metabolites (Allen and Wang, 2014;Blaszczyk et al, 2016;Jung et al, 2014;Kim et al, 2017;Marous et al, 2015;Pierre et al, 2012;Werner et al, 2011), sensing light (Ortiz-Guerrero et al, 2011), and other processes (Barker, 1985;Chang and Frey, 2000;Chen et al, 2001;Cracan and Banerjee, 2012;Gough et al, 2000;Miles et al, 2011;Parks et al, 2013;Romine et al, 2017;Yaneva et al, 2012). The finding that 86% of bacterial species encode at least one cobamidedependent enzyme in their genome (Shelton et al, 2019) demonstrates the prevalence of cobamide-dependent metabolisms. Widespread use of these cofactors can be attributed to their chemical versatility, as they facilitate challenging chemical reactions including radical-initiated rearrangements, methylation reactions, and reductive cleavage of chemical bonds (Banerjee and Ragsdale, 2003;.…”

“…Culture-based studies have shown that only a subset of cobamides supports a given bacterial metabolism, and uptake or production of other cobamides can inhibit growth (Helliwell et al, 2016;Keller et al, 2018;Mok and Taga, 2013;Watanabe et al, 1992;Yan et al, 2018;Yan et al, 2016;Yi et al, 2012). The requirements of bacteria for particular cobamides is notable given the diversity of cobamides present in host-associated and environmental samples (Allen and Stabler, 2008;Girard et al, 2009;Men et al, 2015), coupled with the absence of de novo cobamide biosynthesis in more than half of bacteria (Shelton et al, 2019). Despite the biological relevance of cobamide structure, and the prevalence of cobamide use among bacteria (Degnan et al, 2014a;Rodionov et al, 2003;Shelton et al, 2019;Zhang et al, 2009), little is understood about the biochemical mechanisms by which cobamides differentially impact microbial physiology.…”