Glycosyltransferase-Mediated Exchange of Rare Microbial Sugars with Natural Products

A large number of plant and microbial architectures have been identified and investigated for potential applications in therapeutics, cosmetics, and nutrition. Nonetheless, continuous identification, and design of novel lead molecules are prerequisites to tackling emerging diseases since most existing drugs are losing utility because of resistance by microorganisms. Advances in biotechnological tools in systems and synthetic biology, chemical biology and metabolic engineering, genome sequencing, and synthesis, protein engineering and mutagenesis have enabled alteration of the biological routes of natural product (NP) biosynthesis in heterologous robust hosts to produce a wide array of compounds (Pandey et al., 2016), thus adding diversity in the NPs. Post-modifications of NPs by tailoring enzymes is one of the promising approaches for engineering and manipulating NPs under human control with selective power. Glycosyltransferases (GTs) have been attracting tremendous attention because of their potential to diversify NPs by conjugating diverse types of sugar appendages (Williams et al., 2007, 2011; Pandey et al., 2014), and altering the physico-chemical and biological properties, such as adsorption, distribution, metabolism, and excretion of molecules (Weymouth-Wilson, 1997). For example, when mycosamine sugar was replaced by perosamine in amphotericin B, antifungal and hemolytic activities were improved in new derivative which has minimal inhibitory activity concentration (MIC) of 1.9 µg/ml compared to 2.1 µg/ml of amphotericin B against Saccharomyces cerevisiae (Hutchinson et al., 2010). Similarly, when D-desosamine of YC-17 was replaced with four sugars D-quinovose, L-rhamnose, L-olivose, and D-boivinose, the L-rhamnose sugar conjugated derivative exhibited better antibacterial activity than the parent YC-17 against erythromycin-susceptible and resistant Enterococcus faecium and Staphylococcus aureus (Shinde et al., 2013). GTs have also been exploited to reverse the glycosylation reactions in NPs (Zhang et al., 2006). This property of GTs expanded the possibility of synthesizing diverse nucleotide diphosphate (NDP)-sugars and exchanging them among different classes of NPs by single vessel trans-glycosylation (Zhang et al., 2014). The application of GTs in the industrial biosynthesis of NP glycosides (De Bruyn et al., 2015), detoxification of pollutants, pesticides, and xenobiotics (Stupp et al., 2013), and homeostasis of plant hormones to control crop engineering (Tiwari et al., 2016) has profound impact on human daily life. Thus, plant and microbial GTs with broad substrate promiscuity have been identified and characterized to glycodiversify NPs to further widen their scope for the generation of future molecules for human use (Elshahawi et al., 2015; Tiwari et al., 2016). Such powerful enzymes can be engaged for the exchange of …