Biotin Biosynthesis

Biotin has an unusual structure (see above figure), with two rings fused together via one of their sides. The two rings are ureido and thiophenemoieties. Biotin is a heterocyclic, S-containing monocarboxylic acid. It is made from two precursors, alanineand pimeloyl-CoA via three enzymes. 8-Amino-7-oxopelargonic acid synthase is a pyridoxal 5'-phosphateenzyme. The pimeloyl-CoA, could be produced by a modified fatty acid pathway involving a malonyl thioester as the starter. 7,8Diaminopelargonic acid (DAPA) aminotransferase is unusual in using S-adenosyl methionine(SAM) as the NH₂ donor. Dethiobiotin synthethase catalyzes the formation of the ureido ring via a DAPA carbamate activated with ATP. Biotin synthase reductively cleaves SAM into a deoxyadenosyl radical—a first radical formed on dethiobiotin is trapped by the sulfur donor, which was found to be the iron-sulfur (Fe-S) center contained in the enzyme.^[11]