Metabolic engineering for bioproduction of sugar alcohols

doi:10.1016/j.copbio.2008.08.002

Current Opinion in Biotechnology

Volume 19, Issue 5, October 2008, Pages 461-467

https://doi.org/10.1016/j.copbio.2008.08.002 Get rights and content

Sugar alcohols find applications in pharmaceuticals, oral and personal care products, and as intermediates in chemical synthesis. While industrial-scale production of these compounds has generally involved catalytic hydrogenation of sugars, microbial-based processes receive increasing attention. The past few years have seen a variety of interesting metabolic engineering efforts to improve the capabilities of bacteria and yeasts to overproduce xylitol, mannitol, and sorbitol. Examples include heterologous expression of yeast xylose reductase in Escherichia coli for the production of xylitol, coexpression of formate dehydrogenase, mannitol dehydrogenase, and a glucose facilitator protein in Corynebacterium glutamicum for mannitol production from fructose and formate, and overexpression of sorbitol-6-phosphate dehydrogenase in lactate dehydrogenase-deficient Lactobacillus plantarum to achieve nearly maximum theoretical yields of sorbitol from glucose.

Introduction

Sugar alcohols are a class of polyols in which sugar's carbonyl (aldehyde or ketone) is reduced to the corresponding primary or secondary hydroxyl group. They have characteristics similar to sugar and are used to improve the nutritional profile of food products owing to health-promoting properties such as lower caloric content, noncariogenicity, and low glycemic index and insulin response [1, 2]. Other auspicious qualities as food additives include high enthalpies of solution and lack of reactive carbonyls. Sugar alcohols additionally find many applications in pharmaceuticals, chemicals production, oral and personal care, and animal nutrition [3]. They are found naturally in fruits and vegetables and are produced by microorganisms, serving as carbohydrate reserves, storage of reducing power, translocatory compounds, and osmoprotectants.

Traditional industrial production of most sugar alcohols is accomplished by hydrogenating sugars over nickel catalysts under high temperature and pressure conditions [2]. Biosynthetic routes offer the potential for safer, environmentally friendly production with enhanced product specificity. Enzyme-based processes for the production of sugar alcohols via sugar reduction have been investigated but are not within the scope of this review. However, costs associated with enzyme preparations and cofactor regeneration for in vitro synthesis of sugar alcohols contribute to the general perception that the use of whole cells presents a more attractive biological approach to produce these compounds from crude sugar feedstocks. Here we review recent metabolic engineering efforts to improve microbial production of the common sugar alcohols xylitol, mannitol, and sorbitol.

Section snippets

Xylitol

Xylitol is a five-carbon sugar alcohol obtained from xylose reduction. The annual xylitol market is estimated to be $340 million, priced at $4–5 kg⁻¹ [4]. Xylitol has received the most recent attention of all the sugar alcohols, particularly as it pertains to microbial production and metabolic engineering. As depicted in Figure 1, yeasts naturally produce xylitol as an intermediate during d-xylose metabolism. Xylose reductase (XR) is typically an NADPH-dependent enzyme, while xylitol

Mannitol

d-Mannitol is a six-carbon sugar alcohol with a variety of clinical applications, in addition to its use as a sweetener. It is produced by a variety of organisms including bacteria and plants, and Candida magnoliae has been used for the industrial production of mannitol [29]. Other organisms currently targeted as microbial hosts for mannitol production include lactic acid bacteria (LAB), E. coli, Bacillus megaterium, S. cerevisiae, and Corynebacterium glutamicum. Metabolic engineering efforts

Sorbitol

d-Sorbitol (d-glucitol) is a popular six-carbon sugar alcohol (a stereoisomer of mannitol) with an estimated annual production of over 500,000 tons and finding applications in the food industry and as a building block for pharmaceutical products [3]. Early studies of biotechnological production of sorbitol primarily focused on the bacterium Z. mobilis, which naturally can convert fructose and glucose to sorbitol (via glucose–fructose oxidoreductase) for osmoprotection [3, 43].

The ability of the

Conclusions

Microbial production of xylitol, mannitol, and sorbitol has received considerable attention in recent years, and the metabolic engineering strategies addressed in this review are summarized in Table 1. Although many organisms naturally produce these compounds, genetic modification strategies have allowed for their enhanced production. LAB have been particularly exploited in that regard. Alternately, organisms that do not naturally produce a sugar alcohol have been provided the facilities to do

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgement

We thank the National Science Foundation for financial support (grant no. BES0519516).

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¹: These authors contributed equally to this work.

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Metabolic engineering for bioproduction of sugar alcohols

Introduction

Section snippets

Xylitol

Mannitol

Sorbitol

Conclusions

References and recommended reading

Acknowledgement

J Biosci Bioeng

Curr Opin Biotechnol

Chem Biol Interact

Enzyme Microb Technol

J Mol Catal B: Enzym

J Mol Catal B: Enzym

Biotechnol Bioeng

Biotechnol Prog

Int Dairy J

J Biotechnol

Appl Environ Microbiol

J Bacteriol

Eur J Biochem

A rare sugar xylitol. Part I. The biochemistry and biosynthesis of xylitol

Appl Microbiol Biotechnol

Sugar alcohols

The biotechnological production of sorbitol

Appl Microbiol Biotechnol

Flexible biorefinery for producing fermentation sugars, lignin and pulp from corn stover

J Ind Microbiol Biotechnol

Xylitol conversion by fermentation using five yeast strains and polyelectrolyte-assisted ultrafiltration

Biotechnol Lett

A rare sugar xylitol. Part II. Biotechnological production and future applications of xylitol

Appl Microbiol Biotechnol

Enhancement of xylitol productivity and yield using a xylitol dehydrogenase gene-disrupted mutant of Candida tropicalis under fully aerobic conditions

Biotechnol Lett

Xylitol production by a Pichia stipitisd-xylulokinase mutant

Appl Microbiol Biotechnol

The expression of a Pichia stipitis xylose reductase mutant with higher KM for NADPH increases ethanol production from xylose in recombinant Saccharomyces cerevisiae

Biotechnol Bioeng

Xylose transport studies with xylose-utilizing Saccharomyces cerevisiae strains expressing heterologous and homologous permeases

Appl Microbiol Biotechnol

The expression of a Pichia stipitis xylose reductase mutant with higher K_M for NADPH increases ethanol production from xylose in recombinant Saccharomyces cerevisiae