Early Stage of Biotin Biosynthesis Pathway: Non‐Conserved Yet Unique

Biotin is an essential cofactor across the three domains of life. Since humans lack the de novo synthesis of biotin, bacterial biotin synthesis pathway is an attractive target for the development of new antibacterial. The pathway is divided into two phases: the early and late segments. The late stage of biotin biosynthesis is a conserved pathway in which biotin is synthesized from a pimelate precursor using four conserved enzymes, whereas the early stage remained largely unknown until its discovery in Escherichia coli in 2010. Since then, the early stage of biotin biosynthesis has emerged as divergent and varies among different species. In this review, the early stage of biotin biosynthesis and its diversity across species is discussed. The review also highlights the structural biology of the enzymes involved in generating the pimelate moiety, the precursor molecule utilized in the late stage to synthesize biotin molecules.