Cyclase

About: Cyclase is a research topic. Over the lifetime, 10162 publications have been published within this topic receiving 388566 citations.

Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides.

Abstract: Δ9-Tetrahydrocannabinol (THC) and other cannabinoids are responsible for the psychoactive and medicinal properties of Cannabis sativa L. (marijuana). The first intermediate in the cannabinoid biosynthetic pathway is proposed to be olivetolic acid (OA), an alkylresorcinolic acid that forms the polyketide nucleus of the cannabinoids. OA has been postulated to be synthesized by a type III polyketide synthase (PKS) enzyme, but so far type III PKSs from cannabis have been shown to produce catalytic byproducts instead of OA. We analyzed the transcriptome of glandular trichomes from female cannabis flowers, which are the primary site of cannabinoid biosynthesis, and searched for polyketide cyclase-like enzymes that could assist in OA cyclization. Here, we show that a type III PKS (tetraketide synthase) from cannabis trichomes requires the presence of a polyketide cyclase enzyme, olivetolic acid cyclase (OAC), which catalyzes a C2–C7 intramolecular aldol condensation with carboxylate retention to form OA. OAC is a dimeric α+β barrel (DABB) protein that is structurally similar to polyketide cyclases from Streptomyces species. OAC transcript is present at high levels in glandular trichomes, an expression profile that parallels other cannabinoid pathway enzymes. Our identification of OAC both clarifies the cannabinoid pathway and demonstrates unexpected evolutionary parallels between polyketide biosynthesis in plants and bacteria. In addition, the widespread occurrence of DABB proteins in plants suggests that polyketide cyclases may play an overlooked role in generating plant chemical diversity.

Defect of receptor-cyclase coupling protein in psudohypoparathyroidism.

Abstract: Hormone-sensitive adenylate cyclase contains a recently discovered protein component that is required for stimulation of cyclic AMP synthesis by hormones and guanine nucleotides; the component presumably couples the membrane receptor to the cyclase. We studied this protein (termed "N") in erythrocyte membranes of patients with pseudohypoparathyroidism, using assays of the protein's biochemical activity and of its susceptibility to radiolabeling in the presence of [32P]NAD and cholera toxin. By both assays, the protein's activity was reduced by 40 to 50 per cent in erythrocytes of five of 10 patients with Type I pseudohypoparathyroidism as compared with those of normal and hypoparathyroid subjects and one patient with Type II pseudohypoparathyroidism. If activity of the N protein is reduced in other tissues, this deficiency could cause the resistance of target organs in pseudohypoparathyroidism to parathyroid hormone and other hormones that work via cyclic AMP. Erythrocytes of five patients with Type I pseudohypoparathyroidism, all in one family, showed no defect in activity of the N protein; the biochemical defect of this family remains undefined.