Positive feedback effect of benzodiazepine alkaloids on enzymes of the aromatic pathway

Abstract Penicillium cyclopium produces benzodiazepine alkaloids from l -phenylalanine and anthranilate. The biosynthesis of both precursors involves the enzymes of the shikimate pathway DAHP synthase, chorismate mutase and anthranilate synthase, the latter two competing for the common substrate chorismate. After the cultures reached the phase of alkaloid production, the in vitro measurable activities of these three enzymes could be increased by adding the alkaloids during incubation. The stimulation is most pronounced with anthranilate synthase, whose activity most probably limits the rate of alkaloid formation. It is not seen with tryptophan synthase which is not involved in the formation of alkaloid precursors. The data suggest a far reaching feedback activation, coordinating precursor biosynthesis with the formation of secondary product.