Metabolic engineering for bioproduction of sugar alcohols
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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2020, Biochemical Engineering JournalCitation Excerpt :Based on this, cofactor engineering was taken to enhance ATP and NADH generation. Cofactor regeneration has been proved to be an effective way to maintain the cellular redox balance by altering the intracellular cofactor pool and a number of enzymes have been discovered to directly affect the ratio of NADH/NAD+ or ATP/ADP, such as cytoplasmic H2O-forming NADH oxidase (NOX) [72], mitochondrial alternative oxidase (AOX) [73], phosphoenolpyruvate carboxykinase (PCK) [74], and formate dehydrogenase (FDH) [75]. Therefore, PCK was overexpressed to generate ATP to motivate the RoPYC‐catalyzed carboxylation of pyruvic acid to oxaloacetic acid, and FDH was overexpressed to generate NADH which could be used to drive the RoMDH‐catalyzed reduction of oxaloacetic acid to malic acid.
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These authors contributed equally to this work.