Biosynthesis of rare hexoses using microorganisms and related enzymes

Abstract

Rare sugars, referred to as monosaccharides and their derivatives that rarely exist in nature, can be applied in many areas ranging from foodstuffs to pharmaceutical and nutrition industry, or as starting materials for various natural products and drug candidates. Unfortunately, an important factor restricting the utilization of rare sugars is their limited availability, resulting from limited synthetic methods. Nowadays, microbial and enzymatic transformations have become a very powerful tool in this field. This article reviews the biosynthesis and enzymatic production of rare ketohexoses, aldohexoses and sugar alcohols (hexitols), including D-tagatose, D-psicose, D-sorbose, L-tagatose, L-fructose, 1-deoxy-L-fructose, D-allose, L-glucose, L-talose, D-gulose, L-galactose, L-fucose, allitol, D-talitol, and L-sorbitol. New systems and robust catalysts resulting from advancements in genomics and bioengineering are also discussed.

Keywords: biosynthesis; enzyme; hexose; microorganism; rare sugars.

Scheme 1

Synthesis of D-tagatose from D-galactose using L-arabinose isomerase.

Scheme 2

Synthesis of D-psicose from D-fructose using D-tagatose 3-epimerase/D-psicose 3-epimerase.

Figure 1

The active site in D-psicose 3-epimerase (DPEase) in the presence of D-fructose, showing the metal coordinating site and the substrate-binding site. The purple ball indicates the manganese(II) ion coordinating with key amino acid residues (Glu150, Asp183, His209, and Glu244) and the O-2 and O-3 of fructose. This figure was created using PDB File 2HK1 [38].

Scheme 3

Enzymatic synthesis of D-psicose using aldolase FucA.

Scheme 4

Proposed pathway of the D-sorbose synthesis from galactitol or L-glucitol.

Scheme 5

Simultaneous enzymatic synthesis of D-sorbose and D-psicose.

Scheme 6

Biosynthesis of L-tagatose.

Scheme 7

Preparative-scale synthesis of L-tagatose and L-fructose using aldolase.

Scheme 8

Biosynthesis of L-fructose.

Scheme 9

Preparative-scale synthesis of L-fructose using aldolase RhaD.

Scheme 10

Chemoenzymatically synthesis of 1-deoxy-L-fructose [8].

Scheme 11

Potential enzymes (isomerases) for the bioconversion of D-psicose to D-allose.

Scheme 12

Three-step bioconversion of D-glucose to D-allose.

Scheme 13

Biosynthesis of L-glucose.

Scheme 14

Enzymatic synthesis of L-talose and D-gulose.

Scheme 15

Enzymatic synthesis of L-galactose.

Scheme 16

Enzymatic synthesis of L-fucose.

Scheme 17

Synthesis of allitol from D-fructose using a multi-enzyme system.

Scheme 18

Biosynthesis of D-talitol via C-2 reduction of rare sugars.

Scheme 19

Biosynthesis of L-sorbitol via C-2 reduction of rare sugars.