Biotin catabolism: an unwritten chapter in the metabolism of an essential vitamin

Biotin is an essential vitamin in the human diet. The adequate daily intake for adult
humans is in the range of 30-100 micrograms. The biotin market is divided between agricultural
and human use with 90% and 10% going to animal and human nutrition respectively. Currently
biotin is produced by chemical synthesis at the level of >20 tons/year. Biotin biosynthesis is
well-understood and efforts to produce it by fermentation are currently under intense
investigation in several biotechnology companies. Biotin functions as a cofactor in all
biochemical carboxylation reactions involving bicarbonate as the CO2 donor. The mechanism of
biotin mediated carboxylation is now well-understood. Biotin has also found extensive
applications in chemical biology where the strong biotin avidin interaction has been extensively
used for macromolecular tagging.
In contrast to biotin biosynthesis, little is known about biotin catabolism. A few products of
biotin catabolism in a soil Pseudomonad grown on biotin as the sole carbon source have been
isolated but no genes or enzymes associated with biotin catabolism have yet been identified.
This proposal will focus on the isolation of a biotin catabolic strain, the identification of the
catabolic operon and the reconstitution of all enzymes involved in biotin catabolism. Mechanistic
and structural studies will be carried out on the key enzymes involved in the degradation of the
biotin heterocyclic core.

Grant Number: 5R01GM144755-04
NIH Institute/Center: NIH
Principal Investigator: TADHG BEGLEY