Exclusive production of fluoro-unnatural oxindole alkaloids by transgenic Uncaria guianensis via precursor-directed biosynthesis

• Processo: 16/50463-5
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Data de Início da vigência: 01 de fevereiro de 2017
• Data de Término da vigência: 31 de janeiro de 2019
• Área do conhecimento: Ciências Exatas e da Terra - Química - Química Orgânica
• Proposta de Mobilidade: SPRINT - Projetos de pesquisa - Mobilidade
• Pesquisador responsável: Adriana Aparecida Lopes
• Beneficiário: Adriana Aparecida Lopes
• Instituição Sede: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brasil
• Município da Instituição Sede: Ribeirão Preto
• Vinculado ao auxílio: 13/07349-9 - Alcalóides oxindólicos de Uncaria tomentosa: estudos biossintéticos e obtenção de análogos por biossíntese dirigida pelo precursor, AP.JP
• Assunto(s): Uncaria guianensis Unha-de-gato Triptofano Biossíntese Alcaloides
• Palavra(s)-Chave do Pesquisador: Quimica

Resumo

Natural product derivatives or "unnatural products" are known to play a substantial role in drug discovery. Nowadays, there are about 200 pharmaceuticals fluorine containing into various heterocyclic scaffolds and the presence of fluorine atoms within their structures increase the therapeutic efficacy and pharmacological properties. Metabolic engineering strategies to generate "unnatural" monoterpene indole alkaloids have been successful in medicinal plant Catharanthus roses by Dr. Sarah E. O'Connor's Lab, John Innes Centre, and UK. Mutasynthesis strategies mediated by RNA suppression of tryptamine biosynthesis in Catharanthus roses eliminated production of natural monoterpene indole alkaloids and it was possible to obtain desirable unnatural alkaloid production by supplementation with unnatural tryptamine analogues. Uncaria guianensis biosynthesize oxindole alkaloids, which are known to have biological significance, by the same biosynthetically route as found in vinca alkaloids (Catharanthus roseus). Our goal is carry out RNA silencing of tryptophan decarboxylase (TDC) to suppress the biosynthesis of tryptamine in Uncaria guianensis (Rubiaceae) callus culture in order to obtain novel fluoro-unnatural oxindole alkaloids. The combination of genetic manipulation and precursor-directed biosynthesis using unnatural precursors (fluoro-tryptamine) represents an increasingly viable resource to produce unnatural oxindole alkaloids into transgenic callus culture from U. guianensis. (AU)