Utilization of Cobalamin Is Ubiquitous in Early-Branching Fungal Phyla

Abstract

Cobalamin is a cofactor present in essential metabolic pathways in animals and one of the water-soluble vitamins. It is a complex compound synthesized solely by prokaryotes. Cobalamin dependence is scattered across the tree of life. In particular, fungi and plants were deemed devoid of cobalamin. We demonstrate that cobalamin is utilized by all non-Dikarya fungi lineages. This observation is supported by the genomic presence of both B12-dependent enzymes and cobalamin modifying enzymes. Fungal cobalamin-dependent enzymes are highly similar to their animal homologs. Phylogenetic analyses support a scenario of vertical inheritance of the cobalamin usage with several losses. Cobalamin usage was probably lost in Mucorinae and at the base of Dikarya which groups most of the model organisms and which hindered B12-dependent metabolism discovery in fungi. Our results indicate that cobalamin dependence was a widely distributed trait at least in Opisthokonta, across diverse microbial eukaryotes and was likely present in the LECA.

Diploid-dominant life cycles characterize the early evolution of Fungi

“…Discovery of widespread diploidy in zoosporic fungi parallels recent studies that show interpretation of fungal traits based only on analysis of Dikarya may be misleading ( 4 , 5 , 7 , 8 , 39 ). Many of these misinterpreted traits were those inherited from the Opisthokont MRCA, i.e., are plesiomorphic.…”

“…5 ). Selenoproteins, or proteins containing the 21st amino acid selenocysteine, and cobalamin-associated enzymes are examples of genetic traits that were assumed to be absent from fungi but have been recently detected in EDF ( 7 , 39 ). Both traits are widely distributed in EDF but show different phylogenetic distribution patterns.…”

“…Further, life cycles have not been carefully investigated in most early-diverging fungal lineages (EDF), which include many phyla outside of Dikarya (e.g., non-Dikarya fungi). EDF have retained ancestral traits also retained in Metazoa, such as flagellation, actin structures used for crawling, presence of cholesterol in cell membranes, vitamin dependencies, and cell-cycle genes ( 4 – 8 ). However, life-cycle transitions between the Opisthokont ancestor and the extant Fungi are shrouded due to a lack of information on the genetic characteristics of EDF and the undersampling of their genomic diversity ( 9 – 11 ).…”

The conserved protein CBA1 is required for vitamin B12uptake in different algal lineages

“…Intriguingly, the reverse is observed in the Metazoa, where METH is almost universal, but CBA1 is entirely absent. However, some Choanoflagellates and some species of fungi do appear to encode both METH and CBA1, suggesting that they utilise B 12 , a trait only recently recognised to occur in fungi (Orłowska et al, 2021). It will be of interest therefore to test whether CBA1 is involved in B 12 uptake in these organisms, for example by gene knockout studies.…”

Emerging Trends in Metal‐based Anticancer Agents: Drug Design to Clinical Trials and their Mechanism of Action

“…[95] Cobalamin can only be synthesized by archaea and certain eubacteria via a complex biochemical process. [96] Cobalt-containing compounds have drawn a lot of attention as systemic anticancer therapy because of their detrimental effects on normal cells and tissues. [97] Since the beginning, cobalamin has been utilized in antimetabolite chemotherapy regimens along with folic acid to prevent adverse reactions.…”