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https://hdl.handle.net/1822/64331
Título: | Identification and microbial production of the raspberry phenol salidroside that is active against Huntington's disease |
Autor(es): | Kallscheuer, Nicolai Menezes, Regina Foito, Alexandre Henriques da Silva, Marcelo D. Braga, Adelaide Dekker, Wijbrand Sevillano, David Méndez Rosado-Ramos, Rita Jardim, Carolina Oliveira, Joana Filipa Azevedo Ferreira, Patrícia Rocha, I. Silva, Ana Rita Sousa, M. Allwood, James William Bott, Michael Faria, Nuno Costa Martins de Stewart, Derek Ottens, Marcel Naesby, Michael Santos, Claudia Nunes dos Marienhagen, Jan |
Data: | Mar-2019 |
Editora: | American Society of Plant Biologists |
Revista: | Plant Physiology |
Citação: | Kallscheuer, Nicolai; Menezes, Regina; Foito, Alexandre; Henriques da Silva, Marcelo D.; Braga, Adelaide; Dekker, Wijbrand; Sevillano, David Méndez; Rosado-Ramos, Rita; Jardim, Carolina; Oliveira, J.; Ferreira, Patrícia; Rocha, Isabel; Silva, Ana Rita; Sousa, M.; Allwood, James William; Bott, Michael; Faria, N.; Stewart, Derek; Ottens, Marcel; Naesby, Michael; Santos, Claudia Nunes dos; Marienhagen, Jan, Identification and microbial production of the raspberry phenol salidroside that is active against Huntington's disease. Plant Physiology, 179(3), 969-985, 2019 |
Resumo(s): | Edible berries are considered to be among nature's treasure chests as they contain a large number of (poly)phenols with potentially health-promoting properties. However, as berries contain complex (poly)phenol mixtures, it is challenging to associate any interesting pharmacological activity with a single compound. Thus, identification of pharmacologically interesting phenols requires systematic analyses of berry extracts. Here, raspberry (Rubus idaeus, var. Prestige) extracts were systematically analyzed to identify bioactive compounds against pathological processes of neurodegenerative diseases. Berry extracts were tested on different Saccharomyces cerevisiae strains expressing disease proteins associated with Alzheimer's, Parkinson's, or Huntington's disease or amyotrophic lateral sclerosis. After identifying bioactivity against Huntington's disease, the extract was fractionated and the obtained fractions were tested in the yeast model, which revealed that salidroside, a glycosylated phenol, displayed significant bioactivity. Subsequently, a metabolic route to salidroside was reconstructed in S. cerevisiae and Corynebacterium glutamicum. The best-performing S. cerevisiae strain was capable of producing 2.1 mM (640 mg L-1) salidroside from glucose in shake flasks, whereas an engineered C. glutamicum strain could efficiently convert the precursor tyrosol to salidroside, accumulating up to 32 mM (9,700 mg L-1) salidroside in bioreactor cultivations (yield: 0.81 mol mol-1). Targeted yeast assays verified that salidroside produced by both organisms has the same positive effects as salidroside of natural origin. |
Tipo: | Artigo |
Descrição: | Sequence data from this article can be found in the GenBank/EMBL data libraries under accession numbers: KX262844.1 (RsUGT72B14, R. sachalinensis); AY547304.1 (RsUGT73B6. R. sachalinensis); NP_418458.1 (malE, E. coli); NP_415214.1 (pgm, E. coli); NP_415752.1 (galU, E. coli); NM_001180688.3 (aro10, S. cerevisiae), and NP_417484.1 (yqhD, E. coli). |
URI: | https://hdl.handle.net/1822/64331 |
DOI: | 10.1104/pp.18.01074 |
ISSN: | 0032-0889 |
e-ISSN: | 1532-2548 |
Versão da editora: | http://www.plantphysiol.org/ |
Arbitragem científica: | yes |
Acesso: | Acesso restrito UMinho |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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document_49120_1.pdf Acesso restrito! | 2,42 MB | Adobe PDF | Ver/Abrir |