Recently, Krief et al.^[1] reported the schizophrenic behavior of oxidosqualene sterol cyclase from pig liver towards 2,3-oxidosqualene analogs bearing two alkyl groups different from a methyl.

The topic of this work is the relatively limited area of squalene cyclization and its rather small aspects of steroid synthesis, but it is the most important biological^[2] synthesis of human beings because it is the starting point of steroid synthesis. There are several mysteries of this selectivity, and the topic of this paper is one of the most important steps of biosynthesis. This paper clearly shows the reason for these mysterious issues. The final stage of cyclization generates the necessary rotation of the C-C bond to create the necessary stereochemistry of the product steroid^[3]. The authors nicely used the different size of the alkyl group to explain the biological synthesis of steroids.

The paper “Schizophrenic behavior of 2,3-Oxidosqualene Sterol Cyclase from pig liver towards 2,3-oxidosqualene analogues” is outstanding because it solves the long-standing problem of sterol biosynthesis. Congratulations for a great contribution!