Identification and Microbial Production of the Raspberry Phenol Salidroside that Is Active against Huntington’s Disease

Abstract

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 21 ) salidroside from Glc 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 21 ) salidroside in bioreactor cultivations (yield: 0.81 mol mol 21 ). Targeted yeast assays verified that salidroside produced by both organisms has the same positive effects as salidroside of natural origin.

Antioxidative Activity of 1,3,5-Triazine Analogues Incorporating Aminobenzene Sulfonamide, Aminoalcohol/Phenol, Piperazine, Chalcone, or Stilbene Motifs

“…Antioxidants possess great potential as drugs suitable for the treatment of various diseases related to oxidative stress. In particular, the use of compounds containing phenol structural moiety in the treatment of Alzheimer's disease [32][33][34][35][36], Parkinson´s disease [37][38][39], Huntington´s disease [40,41], and cancer [42][43][44][45] have been extensively studied in the last two years. Their structural diversity provides many possibilities for the design and synthesis of new, highly effective agents.…”

<p>Salidroside Alleviates Cartilage Degeneration Through NF-κB Pathway in Osteoarthritis Rats</p>

“…17 For example, Kallscheuer et al found that Sal had a positive therapeutic effect on Huntington's disease. 18 Qin et al declared that Sal was a platinum sensitizer to improve the efficacy of chemotherapy for liver cancer. 19 In OA, Liu et al found that Sal alleviated the inflammatory injury induced by LPS through regulating miR-145.…”

Bioprocess Optimization for the Production of Aromatic Compounds With Metabolically Engineered Hosts: Recent Developments and Future Challenges

“…In general, these processes have a lower environment impact and are able to produce high quality final products when compared to their plant extraction and/or chemical synthesis counterparts (Thompson et al, 2015;Dudnik et al, 2017;Kallscheuer et al, 2019).…”

“…Escherichia coli and Saccharomyces cerevisiae are the most commonly employed microorganisms for aromatic compound production. However, more recently, other hosts have also been explored due to their peculiarities, such as Corynebacterium glutamicum, Lactococcus lactis, Pseudomonas putida, and Streptomyces lividans (Sachan et al, 2006;Gosset, 2009;Verhoef et al, 2009;Gaspar et al, 2016;Kallscheuer et al, 2016Kallscheuer et al, , 2019Dudnik et al, 2017Dudnik et al, , 2018Braga et al, 2018a;Tilburg et al, 2019).…”