title: Carnosic acid biosynthesis elucidated by a synthetic biology platform.
abstract: Synthetic biology approaches achieving the reconstruction of specific plant natural product biosynthetic pathways in dedicated microbial "chassis" have provided access to important industrial compounds (e.g., artemisinin, resveratrol, vanillin). However, the potential of such production systems to facilitate elucidation of plant biosynthetic pathways has been underexplored. Here we report on the application of a modular 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.Four cytochrome P450 enzymes are identified (CYP76AH24, CYP71BE52, CYP76AK6, and CYP76AK8), the combined activities of which account for all of the oxidation events leading to the biosynthesis of the major diterpenes produced in these plants. This approach develops yeast as an efficient tool to harness the biotechnological potential of the numerous sequencing datasets that are increasingly becoming available through transcriptomic or genomic studies.
authors.affiliation: Department of Biochemistry, School of Medicine, University of Crete, Heraklion 71003, Greece;
authors.forename: Codruta
authors.initials: C
authors.lastname: Ignea
authors.affiliation: Department of Biochemistry, School of Medicine, University of Crete, Heraklion 71003, Greece;
authors.forename: Anastasia
authors.initials: A
authors.lastname: Athanasakoglou
authors.affiliation: Department of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Athens 15771, Greece;
authors.forename: Efstathia
authors.initials: E
authors.lastname: Ioannou
authors.affiliation: Department of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Athens 15771, Greece;
authors.forename: Panagiota
authors.initials: P
authors.lastname: Georgantea
authors.affiliation: Institute of Applied Biosciences-Centre for Research and Technology Hellas, Thermi 57001, Thessaloniki, Greece;
authors.forename: Fotini A
authors.initials: FA
authors.lastname: Trikka
authors.affiliation: Mediterranean Agronomic Institute of Chania, Chania 73100, Greece.
authors.forename: Sofia
authors.initials: S
authors.lastname: Loupassaki
authors.affiliation: Department of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Athens 15771, Greece;
authors.forename: Vassilios
authors.initials: V
authors.lastname: Roussis
authors.affiliation: Institute of Applied Biosciences-Centre for Research and Technology Hellas, Thermi 57001, Thessaloniki, Greece;
authors.forename: Antonios M
authors.initials: AM
authors.lastname: Makris
authors.affiliation: Department of Biochemistry, School of Medicine, University of Crete, Heraklion 71003, Greece; s.kampranis@med.uoc.gr.
authors.forename: Sotirios C
authors.identifier: http://orcid.org/0000-0001-6208-1684
authors.initials: SC
authors.lastname: Kampranis
mesh_terms: D045784:Abietanes / Q000096:biosynthesis* / Q000737:chemistry; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D053898:Biosynthetic Pathways; D001709:Biotechnology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D060847:Metabolic Engineering; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D027542:Rosmarinus / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D027544:Salvia / Q000235:genetics / Q000378:metabolism; D058615:Synthetic Biology / Q000379:methods
chemical_list: D045784:Abietanes; D000975:Antioxidants; D010940:Plant Proteins; D011994:Recombinant Proteins; D003577:Cytochrome P-450 Enzyme System; C018381:salvin
keywords: cytochrome P450; metabolic engineering; terpene; yeast