Codon optimization, not gene content, predicts XYLose metabolism in budding yeasts

Abstract

Xylose is the second most abundant monomeric sugar in plant biomass. Consequently, xylose catabolism is an ecologically important trait for saprotrophic organisms, as well as a fundamentally important trait for industries that hope to convert plant mass to renewable fuels and other bioproducts using microbial metabolism. Although common across fungi, xylose catabolism is rare within Saccharomycotina, the subphylum that contains most industrially relevant fermentative yeast species. Several yeasts unable to consume xylose have been previously reported to possess complete predicted xylolytic metabolic pathways, suggesting the absence of a gene-trait correlation for xylose metabolism. Here, we measured growth on xylose and systematically identify XYL pathway orthologs across the genomes of 332 budding yeast species. We found that most yeast species possess complete predicted xylolytic pathways, but pathway presence did not correlate with xylose catabolism. We then quantified codon usage bias of XYL genes and found that codon optimization was higher in species able to consume xylose. Finally, we showed that codon optimization of XYL2, which encodes xylitol dehydrogenase, positively correlated with growth rates in xylose medium. We conclude that gene content cannot predict xylose metabolism; instead, codon optimization is now the best predictor of xylose metabolism from yeast genome sequence data. Significance StatementIn the genomic era, strategies are needed for the prediction of metabolic traits from genomic data. Xylose metabolism is an industrially important trait, but it is not found in most yeast species heavily used in industry. Because xylose metabolism appears rare across budding yeasts, we sought to identify a computational means of predicting which species are capable of xylose catabolism. We did not find a relationship between gene content and xylose metabolism traits. Rather, we found that codon optimization of xylolytic genes was higher in species that can metabolize xylose, and that optimization of one specific gene correlated with xylose-specific growth rates. Thus, codon optimization is currently the only means of accurately predicting xylose metabolism from genome sequence data.