Microbial production of natural and non-natural flavonoids: Pathway engineering, directed evolution and systems/synthetic biology.

Biotechnological advances in UDP-sugar based glycosylation of small molecules

The glycosylation of bioactive compounds, such as flavonoids, is of particular relevance, as it modulates many of their pharmacokinetic parameters. This article reviews the literature between 2010 and the end of 2015 that deals with the enzymatic O-glycosylation of this class of compounds. Enzymes of glycosyltransferase family 1 remain the biocatalysts of choice for glycodiversification of flavonoids, in spite of relatively low yields. Transfers of 14 different sugars, in addition to glucose, were reported. Several Escherichia coli strains were metabolically engineered to enable a (more efficient) synthesis of the required donor during in vivo glycosylations. For the transfer of glucose, enzymes of glycoside hydrolase families 13 and 70 were successfully assayed with several flavonoids. The number of acceptor substrates and of regiospecificities characterized so far is smaller than for glycosyltransferases. However, their glycosyl donors are much cheaper and yields are considerably higher. A few success stories of enzyme engineering were reported. These improved the catalytic efficiency as well as donor, acceptor, or product ranges. Currently, the development of appropriate high-throughput screening systems appears to be the major bottleneck for this powerful technology.

Recent developments in the enzymatic O-glycosylation of flavonoids

Exploiting the aglycon promiscuity of glycosyltransferase Bs-YjiC from Bacillus subtilis and its application in synthesis of glycosides.

Flavonoids are plant secondary metabolites containing several hydroxyl groups that are targets for modification reactions such as methylation and glycosylation. In plants, flavonoids are present as glycones. Although glucose is the most common sugar attached to flavonoids, arabinose, galactose, glucuronic acid, rhamnose, and xylose are also linked to flavonoids. Depending on the kind and the position of the attached sugar, flavonoid glycones show different biological properties. Flavonoid-O-glycosides are synthesized by uridine diphosphate-dependent glycosyltransferases (UGTs), which use nucleotide sugar as a sugar donor and a diverse compound as a sugar acceptor. Recently, diverse flavonoid-O-glycosides have been synthesized in Escherichia coli by introducing UGTs from plants and bacteria and modifying endogenous pathways. The nucleotide sugar biosynthesis pathway in E. coli has been engineered to provide the proper nucleotide sugar for flavonoid-O-glycoside biosynthesis. In this review, we will discuss recent advances in flavonoid-O-glycoside biosynthesis using engineered E. coli.

Biosynthesis and production of glycosylated flavonoids in Escherichia coli : current state and perspectives

Assessing acceptor substrate promiscuity of YjiC-mediated glycosylation toward flavonoids

. Mangosteen ( Garcinia mangostana L.) peel contains some secondary metabolites, such as xanthones. The present study aimed to investigate the effect of extract from mangosteen peel on the potential weight loss and reducing adipose tissue mass in mice. Male mice fed an high-fat diet (HFD) for 8 weeks were supplemented with mangosteen peel extract (ME) (200 mg/kg/day) for an additional 6 weeks while mice fed a standard diet (SD) were used as normal controls. The results revealed that ME treatment decreased body weight and fat mass including visceral adipose tissue, epididymal white adipose tissue, subcutaneous adipose tissue . The results suggest that ME is effective in reducing weight and adipose tissue mass in HFD-fed mice.

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Papers

Assessing acceptor substrate promiscuity of YjiC-mediated glycosylation toward flavonoids

EFFECT OF MANGOSTEEN (Garcinia mangostana L.) PEEL EXTRACT ON WEIGHT LOSS AND ADIPOSE TISSUE MASS IN MICE