Investigations of the biosynthesis of novobiocin

The biosynthesis of novobiocin was investigated using isotopically labelled compounds. The amino-group of the coumarin unit was found to be derived from tyrosine, other typical 7-oxycoumarin precursors were not incorporated into the coumarin unit of novobiocin, 4′-hydroxyphenylpyruvate was a better precursor of the substituted benzoic acid unit than was 4′-hydroxycinnamic acid. A biosynthetic route to this unit of novobiocin is suggested. Synthetic pathways for 2′,4′-dihydroxyphenylalanine-1-14C and 4-hydroxybenzaldehyde-U-14C are reported for the first time.