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 L21) 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 L21) salidroside in bioreactor cultivations (yield: 0.81 mol mol21). Targeted yeast assays verified that salidroside produced by both organisms has the same positive effects as salidroside of natural origin.

Liquid-liquid extraction (LLE) can be an effective strategy for the purification of polyphenols from a fermentation broth. However, solvents need to be chosen to ensure high extraction capacity and selectivity. For that purpose, a systematic study is here presented, where the partition of different polyphenols - naringin, naringenin, p-coumaric acid, and trans-resveratrol - was measured in different solvents and solvent mixtures and described using the semipredictive NRTL-SAC model. The minimum average absolute deviation obtained, based on predicted activity coefficients, was of 40%. With the exception of naringin, the NRTL-SAC molecular descriptors were estimated using solubility data already available in the literature. The obtained results made it possible to propose suitable LLE-based downstream process schemes for two possible purification scenarios: the recovery of trans-resveratrol and the purification of both naringenin and trans-resveratrol, two similar hydrophobic polyphenols, both from a fermentation broth containing hydrophilic impurities (e.g., sugars, proteins).

BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project.