TY - JOUR
T1 - Phylogenomic analyses of nucleotide-sugar biosynthetic and interconverting enzymes illuminate cell wall composition in fungi
AU - Schwerdt, Julian
AU - Qiu, Hao
AU - Shirley, Neil
AU - Little, Alan
AU - Bulone, Vincent
PY - 2021/4
Y1 - 2021/4
N2 - The fungi are an enormously successful eukaryotic lineage that has colonized every aerobic habitat on Earth. This spectacular expansion is reflected in the dynamism and diversity of the fungal cell wall, a matrix of polysaccharides and glycoproteins pivotal to fungal life history strategies and a major target in the development of antifungal compounds. Cell wall polysaccharides are typically synthesized by Leloir glycosyltransferases, enzymes that are notoriously difficult to characterize, but their nucleotide-sugar substrates are well known and provide the opportunity to inspect the monosaccharides available for incorporation into cell wall polysaccharides and glycoproteins. In this work, we have used phylogenomic analyses of the enzymatic pathways that synthesize and interconvert nucleotide-sugars to predict potential cell wall monosaccharide composition across 491 fungal taxa. The results show a complex evolutionary history of these cell wall enzyme pathways and, by association, of the fungal cell wall. In particular, we see a significant reduction in monosaccharide diversity during fungal evolution, most notably in the colonization of terrestrial habitats. However, monosaccharide distribution is also shown to be varied across later-diverging fungal lineages. IMPORTANCE This study provides new insights into the complex evolutionary history of the fungal cell wall. We analyzed fungal enzymes that convert sugars acquired from the environment into the diverse sugars that make up the fundamental building blocks of the cell wall. Species-specific profiles of these nucleotide-sugar interconverting (NSI) enzymes for 491 fungi demonstrated multiple losses and gains of NSI proteins, revealing the rich diversity of cell wall architecture across the kingdom. Pragmatically, because cell walls are essential to fungi, our observations of variation in sugar diversity have important implications for the development of antifungal compounds that target the sugar profiles of specific pathogens.
AB - The fungi are an enormously successful eukaryotic lineage that has colonized every aerobic habitat on Earth. This spectacular expansion is reflected in the dynamism and diversity of the fungal cell wall, a matrix of polysaccharides and glycoproteins pivotal to fungal life history strategies and a major target in the development of antifungal compounds. Cell wall polysaccharides are typically synthesized by Leloir glycosyltransferases, enzymes that are notoriously difficult to characterize, but their nucleotide-sugar substrates are well known and provide the opportunity to inspect the monosaccharides available for incorporation into cell wall polysaccharides and glycoproteins. In this work, we have used phylogenomic analyses of the enzymatic pathways that synthesize and interconvert nucleotide-sugars to predict potential cell wall monosaccharide composition across 491 fungal taxa. The results show a complex evolutionary history of these cell wall enzyme pathways and, by association, of the fungal cell wall. In particular, we see a significant reduction in monosaccharide diversity during fungal evolution, most notably in the colonization of terrestrial habitats. However, monosaccharide distribution is also shown to be varied across later-diverging fungal lineages. IMPORTANCE This study provides new insights into the complex evolutionary history of the fungal cell wall. We analyzed fungal enzymes that convert sugars acquired from the environment into the diverse sugars that make up the fundamental building blocks of the cell wall. Species-specific profiles of these nucleotide-sugar interconverting (NSI) enzymes for 491 fungi demonstrated multiple losses and gains of NSI proteins, revealing the rich diversity of cell wall architecture across the kingdom. Pragmatically, because cell walls are essential to fungi, our observations of variation in sugar diversity have important implications for the development of antifungal compounds that target the sugar profiles of specific pathogens.
KW - Biosynthesis
KW - Carbohydrates
KW - Evolution
KW - Fungal cell wall
KW - Nucleotide-sugar biosynthesis
KW - Phylogenomic analysis
UR - http://www.scopus.com/inward/record.url?scp=85103982566&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/ARC/DP160100309
U2 - 10.1128/mBio.03540-20
DO - 10.1128/mBio.03540-20
M3 - Article
C2 - 33849982
AN - SCOPUS:85103982566
SN - 2161-2129
VL - 12
JO - mBio
JF - mBio
IS - 2
M1 - e03540-20
ER -