Microbial synthesis of health-promoting inositols

Inositol (cyclohexane-1,2,3,4,5,6-hexanol) is a group of cyclic sugar alcohols. Epimerization of the six hydroxyl groups results in nine stereoisomers (Figure 1). For their analysis, various methods have been reported, such as gas chromatography or HPLC 1, 2. myo-Inositol is the most abundant inositol in nature and available at a much lower price than the rare inositols. Its worldwide production is about 15 000 tons per year [3]. The major industrial production method nowadays is a chemical process removing the phosphate groups of phytate, but various alternative biotechnological processes for myo-inositol production have been described, either by fermentation or by in vitro enzymatic production [3].

myo-Inositol is commonly found in the brain and other mammalian tissues and is known to mediate various cell signaling pathways and plays an indispensable role as the structural basis for various inositol phosphates that function as secondary messengers in eukaryotic cells 4, 5. Furthermore, myo-inositol is a component of phosphatidylinositol phospholipids in cell membranes. As a result, inositol bound to lipids is found in many foods [6]. myo-Inositol was previously considered to belong to the vitamin-B complex and was also called vitamin B8. However, myo-inositol was later found to be produced from glucose in the human body and is therefore no longer considered an essential nutrient [7]. In plants, myo-inositol also has a variety of functions in metabolism and phytic acid, the hexaphosphate of myo-inositol, serves as a phosphate reservoir, and is accumulated in nuts, legumes, and bran-rich cereals [8]. In prokaryotes, myo-inositol plays functional roles in Archaea and actinobacteria [5].

Other naturally found inositol stereoisomers beside myo-inositol are scyllo-, muco-, D-chiro-, L-chiro, allo-, epi-, and neo-inositol [9]. Because they are all rare, no cheap production method has been established yet. cis-Inositol has not been found in nature [9]. scyllo-Inositol prevents the development of amyloid-beta plaques in the brains of transgenic mice, reversing memory impairment. Thus, scyllo-inositol has shown promise as a treatment for Alzheimer's disease [10]. D-chiro-inositol and its 3-O-methyl derivative, D-pinitol, have an insulin-mimetic activity to lower blood glucose levels. The latter compounds are investigated for potential applications in treatments of diabetes and polycystic ovary syndrome 6, 11, 12.

As scyllo-inositol and D-chiro-inositol have demonstrated health benefits, these molecules are promising candidates for functional food additives, and this review describes the development of efficient production of these isomers by two bacteria regarded generally as safe, namely Bacillus subtilis and Corynebacterium glutamicum.

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