title: Correlation of camptothecin-producing ability and phylogenetic relationship in the genus Ophiorrhiza.
abstract: Camptothecin (CPT) is an essential precursor of semisynthetic chemotherapeutic agents for cancers throughout the world. In spite of the rapid growth of market demand, CPT raw material is still harvested by extraction from Camptotheca acuminata and Nothapodytes foetida because its total synthesis is not cost-effective. In this study, we examined eight species of the genus Ophiorrhiza (Rubiaceae) from Thailand as novel alternative sources of CPT. CPT and/or 9-methoxy camptothecin (9-MCPT) were detected at different amounts in the leaf and root extracts of five species. We found that the CPT production ability of Ophiorrhiza spp. in Thailand was related mainly to species, not habitat. Chloroplast MATK and nuclear TOPI genes of eight species were investigated and compared with those of other Ophiorrhiza sequences from GenBank in order to classify and study the evolution in this genus. The molecular phylogenetic trees of both separated and combined MATK and TOPI nucleotide sequences revealed a major clade of Ophiorrhiza taxa correlated with production of CPT and its derivatives. Several amino acid markers of CPT- or 9-MCPT-producing Ophiorrhiza plants were also suggested from the alignment of TopI amino acid sequences. Our findings suggest that genetic factors play an important role in determining the CPT- and 9-MCPT-producing properties of Ophiorrhiza plants. Consequently, MATK and TOPI gene sequences could be utilized for the prediction of CPT and 9-MCPT production ability of members of Ophiorrhiza.
authors.affiliation: Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Varalee
authors.initials: V
authors.lastname: Viraporn
authors.forename: Mami
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Kazuki
authors.initials: K
authors.lastname: Saito
authors.forename: Jessada
authors.initials: J
authors.lastname: Denduangboripant
authors.forename: Kongkanda
authors.initials: K
authors.lastname: Chayamarit
authors.forename: Taksina
authors.initials: T
authors.lastname: Chuanasa
authors.forename: Suchada
authors.initials: S
authors.lastname: Sukrong
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002166:Camptothecin / Q000031:analogs & derivatives / Q000096:biosynthesis*; D002736:Chloroplasts / Q000235:genetics; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D010940:Plant Proteins / Q000235:genetics; D019666:Rubiaceae / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D013045:Species Specificity; D013785:Thailand
chemical_list: D010940:Plant Proteins; C025724:9-methoxycamptothecin; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin