Proc. The cost of bringing a new antibiotic from discovery to market is high and return on investment is low. Google Scholar. Monooxygenase involved in the biosynthesis of carnosate, a potent antioxidant labdane-related diterpene natural product (PubMed:26976595). Our Mission. Cell Death Dis . Carnosic acid ( 1) belongs to the labdane-related class of diterpenoids, whose biosynthesis is most probably initiated by a sequential pair of cyclisation reactions. Hence, it is suggested that carnosic acid biosynthesis or its accumulation takes place entirely in young rosemary leaves, while the diterpene molecule is being partly disbursed during leaf development (Bruckner et al., 2014). 172 - 173 °C. Carnosic acid, a phenolic diterpene specific to the Lamiaceae family, is highly abundant in rosemary (Rosmarinus officinalis).Despite numerous industrial and medicinal/pharmaceutical applications of its antioxidative features, this compound in planta and its antioxidant mechanism have received little attention, except a few studies of rosemary plants … biosynthesis pathway and thus for resistance . Carnosic acid (CA) is a phenolic diterpenoid mainly found in rosemary and sage. We describe here the elucidation of the complete biosynthetic p … We also discuss the deficiencies in our understanding of the relevant biochem. Dysfunction of the dopamine system has been implicated in different nervous system diseases. Kang K, Tarchick MJ, Yu X et al. Dunstan CA, Noreen Y, Serrano G, Cox PA, Perera P, Bohlin L. Evaluation of some Samoan and Peruvian medicinal plants by prostaglandin biosynthesis and rat ear oedema assays. J Ethnopharmacol 1997;57:35-56. Monooxygenase involved in the biosynthesis of carnosate, a potent antioxidant labdane-related diterpene natural product (By similarity). CA has been reported to possess various health-beneficial activities including antibacterial [ 2, 3 ], anti-tumor [ 4 ], anti-inflammatory [ 5 ], and neuroprotection [ 6 ]. Natl Acad. xyferruginol to carnosic acid are catalysed by the related CYP76AK6-8. Carnosic acid slows photoreceptor degeneration in the Pde6b(rd10) mouse model of retinitis pigmentosa. Singh S, Majumdar DK, Rehan HMS. Specific production of pisiferic acid and salviol was achieved by restricting the promiscuity of a key enzyme, CYP76AH24, through a single-residue substitution (F112L). Here, we report on the application of a modular yeast terpene production platform in the elucidation of the biosynthesis of carnosic acid and related diterpenes. Carnosic acid biosynthesis elucidated by a synthetic biology platform. Carnosic acid biosynthesis elucidated by a synthetic biology platform. The enzyme is found in some members of the Lamiaceae (mint family). Academia.edu is a platform for academics to share research papers. Its oxidation products have been identified as (92), an orange powder, m.p. Monooxygenase involved in the biosynthesis of carnosate, a potent antioxidant labdane-related diterpene natural products (PubMed: 26976595 ). genes for the biosynthesis of carnosic acid opens opportunities for the metabolic engineering of phenolic diterpenes, a class of compounds with potent anti-oxidant, anti-inflammatory and anti-tumour activities. Carnosic acid also increased levels of the antioxidant GSH and phase II enzyme NADP(H)-quinone reductase which help protect cells from chemically-induced carcinogenesis, and enhanced signaling through MAPK pathways including ERK and JNK which are involved in the proliferation and differentiation of cells [40,73,74,75,79]. Carnosic acid biosynthesis elucidated by a synthetic biology platform Proc Natl Acad Sci U S A. diphosphate (GGDP) (1), the first steps of carnosic acid biosynthesis are proposed to proceed via a copalyl diphosphate intermediate (copalyl-DP) (2) provided by copalyl. Carnosic acid biosynthesis elucidated by a synthetic biology platform Codruta Igneaa, Anastasia Athanasakogloua, Efstathia Ioannoub, Panagiota Georganteab, Fotini A. Trikkac, Sofia Loupassakid, Vassilios Roussisb, Antonios M. Makrisc, and Sotirios C. Kampranisa,1,2 aDepartment of Biochemistry, School of Medicine, University of Crete, Heraklion 71003, Greece; bDepartment of … Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast. Carnosic acid biosynthesis elucidated by a synthetic biology platform. Catalyzes the oxidation of 11-hydroxyferruginol to produce carnosate (PubMed: 26976595 ). Carnosic acid (CA) is a phenolic diterpene with anti-tumour, anti-diabetic, antibacterial and neuroprotective properties that is produced by a number of species from several genera of the Lamiaceaefamily, including Salvia fruticosa(Cretan sage) and Rosmarinus officinalis(Rosemary). The biosynthesis pathway of carnosic acid is currently being elucidated. USA 113, 3681–3686 (2016). We also discuss the deficiencies in our understanding of the relevant biochemical processes, and suggest the molecular targets of carnosic acid. It belongs to the largest class of over 50,000 plant secondary metabolites termed terpenoids, also known as isoprenoids or terpenes (Hill and Connoly, 2013). In particular, the enzymatic activities responsible for the first three steps in the pathway have been identified, and the synthesis of the carnosic acid precursor ferruginol was achieved using yeast and Nicotiana benthamiana expression systems ( Božić et al., 2015 ). ... terpene production platform in the characterization of the biosynthetic pathway leading to the potent antioxidant carnosic acid and related diterpenes in Salvia pomifera and Rosmarinus officinalis. First, we determined the tissue distribution of CA in mice, … … unravelled. Background: Antimicrobial resistance represents a serious threat to human health across the globe. 9369 Hirom iHagiwara, Roshan Basnet, Sundari I.Wiyasihati, Kyoko Nakata, Keitaro Hagiwara, Hitoshi Miyazaki, Kaoru Yoshida Carnosic acid inhibits the formation of osteoclasts through attenuation of expression of RANKL PharmaNutrition 2015 3:1-6 194.5 - 195 °C (crystallized from acetic acid). Food Chem. Munne-Bosch, S. and Alegre, L. Drought-induced changes in the redox state of alpha-tocopherol, ascorbate, and the diterpene carnosic acid in chloroplasts of Labiatae species differing in carnosic acid contents. Plant Physiol., 125 (2001), pp. These structures of carnosic acid- family metabolites seem to be derived from ferruginol via miltiradiene and abietatriene (Fig. Because carnosic acid (1) contains a phenolic group, it is often classified among polyphenols. Catalyzes the oxidation of abietatriene to produce ferruginol (PubMed:26020634, PubMed:27703160). Carnosic acid (1) biosynthesis probably follows the ‘biogenetic isoprene rule’ (Ruzicka, 1953) and it can be reasonably presumed that the construction of carnosic acid (1) would involve enzyme-assisted electrophilic elongation, cyclisation and … Sci. VERSION 1. Carnosic acid prevents 6-hydroxydopamine-induced cell death in SH-SY5Y cells via mediation of glutathione synthesis. Carnosic Acid Is a Selective Inhibitor of mPGES-1 within Prostanoid Biosynthesis. Catalyzes the oxidation of 11-hydroxyferruginol to produce carnosate (PubMed:26976595). 539-555. Together, S. officinalis extracts and its ingredients carnosol and carnosic acid inhibit PGE The climate changes expected for the next decades will expose plants to increasing occurrences of combined abiotic stresses, including drought, higher temperatures, and elevated CO2 atmospheric concentrations. DOI: 10.1038/ncomms12942 OPEN Mediates the conversion of miltiradien into miltiradien-20-al (PubMed: 27703160 ). In summary, those DEGs might involve in regulating secondary metabolites, such as flavonoids, rosmarinic acid and carnosic acid. 1b).The presence of small amounts of ferruginol in extracts of the aerial parts of S. pomifera (data not shown) supports this hypothesis. Sci. ... (Orn)), together with the imino acid Pro, and the amides such as glutamine and asparagine . Natl Acad. Rosmarinus officinalis L. (rosemary) is a medicinal plant native to the Mediterranean region and cultivated around the world. Ferruginol and 11-hydroxyferruginol are … The type and concentration(s) of secondary molecule(s) produced by a plant are … The level of dopamine transmission increases in response to any type of reward and by a large number of strongly additive drugs. At Designs for Health we are committed to delivering high quality nutritional supplements, educating health care … In order to elucidate the biosynthesis of these compounds, we proceeded with the analysis of the … [Google Scholar] 16Sahu BD, Rentam KK, Putcha UK, Kuncha M, Veqi GM, Sistla R. Carnosic acid attenuates renal injury in an experimental model of rat cisplatin-induced nephrotoxicity. Besides the therapeutic purpose, it is commonly used as a condiment and food preservative. ( B) The biosynthesis of tanshinone and carnosic acid begins with the cyclization of GGPP ( 12) by a class II diTPS to produce (+) copalyl diphosphate (CPP) ( 13 ), which is in turn converted to miltiradiene ( 14) by a class I diTPS. Carnosic acid (CA) is a phenolic diterpene with anti-tumour, anti-diabetic, antibacterial and neuroprotective properties that is produced by a number of species from several genera of the Lamiaceae family, including Salvia fruticosa (Cretan sage) and Rosmarinus officinalis (Rosemary). Cytochrome P450 oxygenases (CYP76AH22-24) from Rosmarinus officinalisand Salvia fruticosaalready characterized as ferruginol synthases are also able to produce 11-hydroxyferruginol. [PMC free article] [Google Scholar] Zhang Y. et al.. Degradation study of carnosic acid, carnosol, rosmarinic acid, and rosemary extract (Rosmarinus officinalis L.) assessed using HPLC. Carnosic acid (CA, Figure 1 A) is a bioactive phenolic diterpenoid mainly found in rosemary ( Rosmarinus officinalis L.) and sage ( Salvia officinalis L.) leaves [ 1 ]. Due to the plastidial localisation of diterpene synthases, plant diterpenoids normally originate from the plastidic 1-deoxyxylulose-5-phosphate (DXP) pathway. If mPGES-1 would be the only target within prostanoid biosynthesis, carnosic acid should not interfere with the biosynthesis and release of other prostanoids than PGE 2. Aiming to elucidate carnosic acid biosynthesis, we set out to develop yeast as a tool for the rapid functional characterization and screening of terpene-targeting CYP genes revealed by next generation transcriptomic analyses. 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