Microbial production of value-added nutraceuticals

Abstract

Nutraceuticals are important natural bioactive compounds that confer health-promoting and medical benefits to humans. Globally growing demands for value-added nutraceuticals for prevention and treatment of human diseases have rendered nutraceuticals a multi-billion dollar market. However, supply limitations and extraction difficulties from natural sources such as plants, animals or fungi, restrict the large-scale use of nutraceuticals. Metabolic engineering via microbial production platforms has been advanced as an eco-friendly alternative approach for production of value-added nutraceuticals from simple carbon sources. Microbial platforms like the most widely used Escherichia coli and Saccharomyces cerevisiae have been engineered as versatile cell factories for production of diverse and complex value-added chemicals such as phytochemicals, prebiotics, polysaccaharides and poly amino acids. This review highlights the recent progresses in biological production of value-added nutraceuticals via metabolic engineering approaches.

Metabolic engineering of Saccharomyces cerevisiae for de novo production of dihydrochalcones with known antioxidant, antidiabetic, and sweet tasting properties

“…Flavonoids and stilbenoids have both been very popular targets in many metabolic engineering publications and two recent reviews give a good overview of the field (Pandey et al, 2016, Wang et al, 2016). On the other hand, DHCs have been the subject of only three studies.…”

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

“…Moreover, it is one of the best studied organisms, easy to handle, and a much larger set of genetic tools is available for this organism compared to other bacteria (Yu et al 2011;Dobson et al 2012;Chen et al 2013). Furthermore, E. coli has been previously used for heterologous production of polyphenolic compounds (Pandey et al 2016;Wang et al 2016a). …”

“…It is therefore essential to develop a greater knowledge of the decorating enzymes specific to berry bioactives, such as those differentially decorating anthocyanins, flavonols, stilbenes, or condensed tannins. Many genes encoding enzymes involved in flavonol and anthocyanin decoration have already been characterized not only in planta, but also heterologously in microorganisms, such as Escherichia coli and S. cerevisiae (Tohge et al 2005;Luo et al 2007;Pandey et al 2016;Wang et al 2016a).…”

“…whereas the absence is noted with a Phenol explorer database (http://phenol-explorer.eu), b (Chaovanalikit et al 2004), c (Zheng et al 2011), d (Ruiz et al 2010), e (Wang et al 2016b), f (Fredes et al 2014) downstream processing (Wang et al 2016a). The BacHBerry consortium decided to address these challenges and set the following objectives: (1) to systematically analyze the phenolic contents in the large berry germplasm collections available from consortium members, (2) to establish a publicly-available database of transcriptomic and metabolic data obtained from berry bioprospecting within, as well as outside of the project, (3) to discover novel bioactivities in berry extracts against a range of human pathologies, such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS), by high-throughput screening with subsequent identification of functional biomolecules, (4) to identify the corresponding biosynthetic genes and perform functional characterization of the respective gene products, (5) to assay a selection of the biosynthetic genes for functionality in Gram-positive bacterial hosts and use those to construct bacterial cell factories for phenolic production, (6) to improve the production efficiency further by introducing modifications to the host metabolic networks predicted via rational design or computational tools developed within the project, (7) to design and optimize costeffective food-grade methods for extraction of phenolic compounds from bacterial fermentation broth, and (8) to optimize fermentation conditions and subsequently upscale the production to pilot plant levels.…”

Glycolysis and Its Metabolic Engineering Applications

“…[49][50][51][52][53][54][55][56] Aromatic compounds are produced via shikimate pathway in bacteria and their biosynthesis is initiated by the condensation of erythrose 4phosphate (E4P) and PEP to form 3deoxydarabinoheptulosonate7 phosphate (DAHP), which will be further converted to chorismate and subsequently branched into Phe, Tyr, and Trp. Thus, metabolic engineering of aromatic amino acids has first focused on enhancing carbon flux to chorismate.…”