Harnessing Plant Sugar Metabolism for Glycoengineering

Abstract

Plants possess an innate ability to generate vast amounts of sugar and produce a range of sugar-derived compounds that can be utilized for applications in industry, health, and agriculture. Nucleotide sugars lie at the unique intersection of primary and specialized metabolism, enabling the biosynthesis of numerous molecules ranging from small glycosides to complex polysaccharides. Plants are tolerant to perturbations to their balance of nucleotide sugars, allowing for the overproduction of endogenous nucleotide sugars to push flux towards a particular product without necessitating the re-engineering of upstream pathways. Pathways to produce even non-native nucleotide sugars may be introduced to synthesize entirely novel products. Heterologously expressed glycosyltransferases capable of unique sugar chemistries can further widen the synthetic repertoire of a plant, and transporters can increase the amount of nucleotide sugars available to glycosyltransferases. In this opinion piece, we examine recent successes and potential future uses of engineered nucleotide sugar biosynthetic, transport, and utilization pathways to improve the production of target compounds. Additionally, we highlight current efforts to engineer glycosyltransferases. Ultimately, the robust nature of plant sugar biochemistry renders plants a powerful chassis for the production of target glycoconjugates and glycans.

Keywords: carbohydrates; glycoconjugates; glycoengineering; glycosides; metabolic engineering; nucleotide sugars.

Figure 1

Plants encode dramatically more glycosyltransferases than other traditional model organisms used for metabolic engineering. Number of known glycosyltransferases in different model organisms. Data acquired from the Carbohydrate Active EnZYmes (CAZY) Database.

Figure 2

Strategies for nucleotide sugar engineering. Nucleotide sugars serve as a critical input for the production of many important biomolecules. Pathway overexpression, transporter overexpression, transporter knockdowns, and the inclusion of non-native nucleotide sugar biosynthesis pathways are approaches that can be used to improve nucleotide sugar availability for product synthesis.

Figure 3

Autoregulation of plant source–sink relationships. Sucrose serves as the general carbon precursor to all plant growth and development, and an accumulation of sucrose has an inhibitory effect on the photosynthetic efficiency of a plant. Creating additional nucleotide sugar sinks that deplete cellular sucrose levels stimulates photosynthesis and increases plant sucrose production. This innate compensatory effect allows for the engineering of additional sugar sinks without the depletion of precursor sugar substrates.