The GMC superfamily of oxidoreductases revisited: analysis and evolution of fungal GMC oxidoreductases

Abstract

Background: The glucose-methanol-choline (GMC) superfamily is a large and functionally diverse family of oxidoreductases that share a common structural fold. Fungal members of this superfamily that are characterised and relevant for lignocellulose degradation include aryl-alcohol oxidoreductase, alcohol oxidase, cellobiose dehydrogenase, glucose oxidase, glucose dehydrogenase, pyranose dehydrogenase, and pyranose oxidase, which together form family AA3 of the auxiliary activities in the CAZy database of carbohydrate-active enzymes. Overall, little is known about the extant sequence space of these GMC oxidoreductases and their phylogenetic relations. Although some individual forms are well characterised, it is still unclear how they compare in respect of the complete enzyme class and, therefore, also how generalizable are their characteristics. Results: To improve the understanding of the GMC superfamily as a whole, we used sequence similarity networks to cluster large numbers of fungal GMC sequences and annotate them according to functionality. Subsequently, different members of the GMC superfamily were analysed in detail with regard to their sequences and phylogeny. This allowed us to define the currently characterised sequence space and show that complete clades of some enzymes have not been studied in any detail to date. Finally, we interpret our results from an evolutionary perspective, where we could show, for example, that pyranose dehydrogenase evolved from aryl-alcohol oxidoreductase after a change in substrate specificity and that the cytochrome domain of cellobiose dehydrogenase was regularly lost during evolution. Conclusions: This study offers new insights into the sequence variation and phylogenetic relationships of fungal GMC/AA3 sequences. Certain clades of these GMC enzymes identified in our phylogenetic analyses are completely uncharacterised to date, and might include enzyme activities of varying specificities and/or activities that are hitherto unstudied.

Transcriptome analysis and functional validation reveal a novel gene, BcCGF1, that enhances fungal virulence by promoting infection‐related development and host penetration

“…The GMC superfamily is a large and functionally diverse family of oxidoreductases that share a common structural fold. Fungal GMC enzymes of this superfamily that exhibit lignocellulose degradation include aryl-alcohol oxidoreductase, alcohol oxidase, cellobiose dehydrogenase, glucose oxidase, glucose dehydrogenase, pyranose dehydrogenase, and pyranose oxidase (Sutzl et al, 2019). In polyporales, the members of the GMC oxidoreductase superfamily also play a central role in degradation of plant polymers because they generate extracellular H 2 O 2 , acting as the ultimate oxidizer in both white-rot and brown-rot decay (Ferreira et al, 2015).…”

Multi-omics analysis provides insights into lignocellulosic biomass degradation by Laetiporus sulphureus ATCC 52600

“…Regarding the enzymes involved in the oxidative mechanism, AA3_1 CDHs are absent in L. sulphureus, as veri ed in P. placenta, W. cocos, and F. pinicola (31). In turn, a large number of genes coding for AA3_2 (aryl alcohol oxidase and glucose 1-oxidase) and AA3_3 (alcohol oxidase) were identi ed, and the products H 2 O 2 (reduction of oxygen by the oxidases) and hydroquinones (reduction of quinones) can support other enzymes or reactions that are important for the deconstruction of lignocellulose (32). Similarly, AA5_1 glyoxal oxidases and AA6 benzoquinone reductase, which are also involved in the generation of Fenton reagents (33)(34)(35), were identi ed (Additional le 1: Table S1).…”

Transcriptomic Analysis of Two Lentinula edodes Genotypes With Different Cadmium Accumulation Ability

“…The abundance of Le_10010568 was down-regulated in Le4606 and Le4625 after 7 h of Cd exposure. Le_10010568 is a glucose–methanol–choline (GMC) oxidoreductase that is expressed by many organisms and plays an auxiliary roles in lignocellulose degradation in fungi ( Sützl et al, 2019 ). The genes annotated as processing binding functions also participate in DNA synthesis (Le_10000608 , DNA polymerase alpha catalytic subunit), RNA splicing (Le_10010279 , RNA-binding protein prp24), and protein translation ( Le_10002733 , Nam9 protein; Le_10004459 , rRNA processing protein Nop9).…”