Biosynthesis of the antibiotic 2,5-dihydrophenylalanine by Streptomyces arenae

The biosynthesis of L-2,5-dihydrophenylalanine (DHPA) in Streptomyces arenae strain Tü 109 was studied in tracer experiments with [U-14C]- and [1,6-14C]shikimic acid followed by chemical degradation of the labeled product. The results indicate that shikimic acid (II) provides only the ring carbons of DHPA, that the side chain of DHPA is attached at the carbon derived from C-1 of II, and that in the transformation of II into DHPA the asymmetry of the ring of II is preserved, with C-6 of II giving rise to C-6' of DHPA. Both generally 14C-labeled chorismate and prephenate, but not L-[3-14C]serine, are incorporated into DHPA. By preparing and feeding 5,6-dihydro[4-3H]prephenate it was shown that this compound is not an intermediate in the biosynthesis of DHPA. A reaction sequence is proposed for the conversion of prephenate to DHPA, involving an allylic rearrangement, followed by 1,4 reduction of the resulting conjugated diene and a combined decarboxylation/dehydration.