Tailoring trehalose for biomedical and biotechnological applications

Abstract

Trehalose is a non-reducing sugar whose ability to stabilize biomolecules has brought about its widespread use in biological preservation applications. Trehalose is also an essential metabolite in a number of pathogens, most significantly the global pathogen Mycobacterium tuberculosis, though it is absent in humans and other mammals. Recently, there has been a surge of interest in modifying the structure of trehalose to generate analogues that have applications in biomedical research and biotechnology. Non-degradable trehalose analogues could have a number of advantages as bioprotectants and food additives. Trehalose-based imaging probes and inhibitors are already useful as research tools and may have future value in the diagnosis and treatment of tuberculosis, among other uses. Underlying the advancements made in these areas are novel synthetic methods that facilitate access to and evaluation of trehalose analogues. In this review, we focus on both aspects of the development of this class of molecules. First, we consider the chemical and chemoenzymatic methods that have been used to prepare trehalose analogues and discuss their prospects for synthesis on commercially relevant scales. Second, we describe ongoing efforts to develop and deploy detectable trehalose analogues, trehalose-based inhibitors, and non-digestible trehalose analogues. The current and potential future uses of these compounds are discussed, with an emphasis on their roles in understanding and combatting mycobacterial infection.

Artificial Fusion of mCherry Enhances Trehalose Transferase Solubility and Stability

“…1) and include the following: (i) trehalose synthase (TreS) interconverting maltose to trehalose (9); (ii) maltooligosyltrehalose synthase (TreYZ) hydrolyzing maltodextrins to trehalose (10,11); (iii) inverting trehalose phosphorylase (TreP inv ) (12)(13)(14)(15) adding ␣-D-glucose-1-phosphate or (iv) retaining trehalose phosphorylase (TreP ret ) (16)(17)(18)(19) adding ␤-D-glucose-1-phosphate to glucose, producing trehalose and phosphate; (v) trehalose transferase (TreT) using D-glucose and a nucleotide diphosphate (NDP) sugar to produce D-trehalose (20)(21)(22)(23)(24)(25); (vi) trehalose phosphate synthase (OtsA) producing D-trehalose-6-phosphate from D-glucose-6-phosphate and a nucleotide sugar (26)(27)(28)(29)(30). In contrast to trehalose phosphate synthase, the LeLoir glycosyltransferase TreT does not require the use of additional 6-phosphate (OtsA), avoiding sequential dephosphorylation of the nonreducing disaccharides, and therefore is of particular interest for industrial food applications (31,32). Additionally, the selective coupling of sugar donors and unprotected monosaccharide acceptors to nonreducing carbohydrates cannot be achieved by chemical catalysts, while glycosyl hydrolases and transferases enable the transfer of sugar acceptors in a regio-, enantio-, and stereospecific manner (33).…”

Autophagy Function and Regulation in Kidney Disease

“…In vivo bioavailability of trehalose is reduced by the enzyme trehalase, which is expressed in the kidney and intestines. Non-hydrolyzable trehalose analogs, known as lentztrehaloses [170], can be useful in vivo models of renal injury.…”

The trehalose-specific transporter LpqY-SugABC is required for antimicrobial and anti-biofilm activity of trehalose analogues in Mycobacterium smegmatis

“…As discussed recently, trehalose metabolism has received increasing attention as a target for the development of novel anti-tubercular agents. [3,4] Trehalose ( 1 ), a non-mammalian disaccharide, is essential for mycobacterial viability and virulence. Trehalose is responsible for the transport of mycolic acids—long-chain (C 60 –C 90 ), α-branched, β-hydroxy fatty acids—to the exterior of the cell, where they are used to construct the thick, hydrophobic mycobacterial outer membrane, or “mycomembrane.”[5] As shown in Figure 1, cytoplasmic trehalose is converted to trehalose monomycolate (TMM),[6] which is then transported across the plasma membrane by MmpL3.…”