Widespread Sterol Methyltransferase Participates in the Biosynthesis of Both C4?- and C4?-Methyl Sterols

The 4-methyl steranes serve as molecular fossils and are used forstudying both eukaryotic evolution and geological history. The occurrence of 4 alpha-methyl steranes in sediments has long been considered evidence of products of partialdemethylation mediated by sterol methyl oxidases (SMOs), while 4 beta-methyl steranesare attributed entirely to diagenetic generation from 4 alpha-methyl steroids since possiblebiological sources of their precursor 4 beta-methyl sterols are unknown. Here, we reporta previously unknown C4-methyl sterol biosynthetic pathway involving a sterolmethyltransferase rather than the SMOs. We show that both C4 alpha- and C4 beta-methylsterols are end products of the sterol biosynthetic pathway in an endosymbiont ofreef corals,Breviolum minutum,while this mechanism exists not only in dinoflagellates but also in eukaryotes from alveolates,haptophytes, and aschelminthes. Our discovery provides a previously untapped route for the generation of C4-methyl steranes andoverturns the paradigm that all 4 beta-methyl steranes are diagenetically generated from the 4 alpha isomers. This may facilitate theinterpretation of molecular fossils and understanding of the evolution of eukaryotic life in general

Automated summary

The 4-methyl steranes are molecular fossils used to study eukaryotic evolution and geological history. Previously, the presence of 4 alpha-methyl steranes in sediments was considered evidence of partial demethylation mediated by sterol methyl oxidases, while 4 beta-methyl steranes were thought to be entirely generated from 4 alpha-methyl steroids. However, researchers have now discovered a previously unknown biosynthetic pathway involving a sterol methyltransferase. This finding provides a new route for the generation of C4-methyl steranes and challenges the previous understanding.