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Production of bioactive diterpenoids in the euphorbiaceae depends on evolutionarily conserved gene clusters.
King, Andrew J; Brown, Geoffrey D; Gilday, Alison D; Larson, Tony R; Graham, Ian A.
Afiliação
  • King AJ; Centre for Novel Agricultural Products, Department of Biology, University of York, Heslington, York YO10 5DD, United Kingdom.
  • Brown GD; Department of Chemistry, University of Reading, Reading RG6 6AD, United Kingdom.
  • Gilday AD; Centre for Novel Agricultural Products, Department of Biology, University of York, Heslington, York YO10 5DD, United Kingdom.
  • Larson TR; Centre for Novel Agricultural Products, Department of Biology, University of York, Heslington, York YO10 5DD, United Kingdom.
  • Graham IA; Centre for Novel Agricultural Products, Department of Biology, University of York, Heslington, York YO10 5DD, United Kingdom ian.graham@york.ac.uk.
Plant Cell ; 26(8): 3286-98, 2014 Aug.
Article em En | MEDLINE | ID: mdl-25172144
The Euphorbiaceae produce a diverse range of diterpenoids, many of which have pharmacological activities. These diterpenoids include ingenol mebutate, which is licensed for the treatment of a precancerous skin condition (actinic keratosis), and phorbol derivatives such as resiniferatoxin and prostratin, which are undergoing investigation for the treatment of severe pain and HIV, respectively. Despite the interest in these diterpenoids, their biosynthesis is poorly understood at present, with the only characterized step being the conversion of geranylgeranyl pyrophosphate into casbene. Here, we report a physical cluster of diterpenoid biosynthetic genes from castor (Ricinus communis), including casbene synthases and cytochrome P450s from the CYP726A subfamily. CYP726A14, CYP726A17, and CYP726A18 were able to catalyze 5-oxidation of casbene, a conserved oxidation step in the biosynthesis of this family of medicinally important diterpenoids. CYP726A16 catalyzed 7,8-epoxidation of 5-keto-casbene and CYP726A15 catalyzed 5-oxidation of neocembrene. Evidence of similar gene clustering was also found in two other Euphorbiaceae, including Euphorbia peplus, the source organism of ingenol mebutate. These results demonstrate conservation of gene clusters at the higher taxonomic level of the plant family and that this phenomenon could prove useful in further elucidating diterpenoid biosynthetic pathways.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ricinus / Família Multigênica / Genes de Plantas / Diterpenos Idioma: En Revista: Plant Cell Assunto da revista: BOTANICA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ricinus / Família Multigênica / Genes de Plantas / Diterpenos Idioma: En Revista: Plant Cell Assunto da revista: BOTANICA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Reino Unido