J. Microbiol. Biotechnol. (2017), 27(5), 869–877 https://doi.org/10.4014/jmb.1612.12005 Research Article Review jmb Bioconversion Using Lactic Acid Bacteria: Ginsenosides, GABA, and Phenolic Compounds Na-Kyoung Lee1 and Hyun-Dong Paik1,2* 1Department of Food Science and Biotechnology of Animal Resources, 2Bio/Molecular Informatics Center, Konkuk University, Seoul 05029, Republic of Korea Received: December 14, 2016 Revised: February 24, 2017 Lactic acid bacteria (LAB) are used as fermentation starters in vegetable and dairy products Accepted: March 15, 2017 and influence the pH and flavors of foods. For many centuries, LAB have been used to manufacture fermented foods; therefore, they are generally regarded as safe. LAB produce various substances, such as lactic acid, β-glucosidase, and β-galactosidase, making them First published online useful as fermentation starters. Existing functional substances have been assessed as March 15, 2017 fermentation substrates for better component bioavailability or other functions. Representative *Corresponding author materials that were bioconverted using LAB have been reported and include minor Phone: +82-2-2049-6011; ginsenosides, γ-aminobutyric acid, equol, aglycones, bioactive isoflavones, genistein, and Fax: +82-2-455-3082; daidzein, among others. Fermentation mainly involves polyphenol and polysaccharide E-mail: [email protected] substrates and is conducted using bacterial strains such as Streptococcus thermophilus, Lactobacillus plantarum, and Bifidobacterium sp. In this review, we summarize recent studies of pISSN 1017-7825, eISSN 1738-8872 bioconversion using LAB and discuss future directions for this field. Copyright© 2017 by The Korean Society for Microbiology Keywords: Lactic acid bacteria, fermentation, bioconversion, phenolic compound, β-glucosidase and Biotechnology Introduction be selected for their potential nutritional benefits. Traditional yogurt starter cultures include Streptococcus thermophilus Consumers have become increasingly concerned about and Lactobacillus delbrueckii sp. bulgaricus. Currently, a healthy and functional foods. The health-food industry has number of dairy products are marketed as containing attempted to identify new materials or utilize existing probiotic bacteria such as L. acidophilus or Bifidobacterium materials in new ways. Intestinal bacteria are involved in species. Fermented tea containing LAB is thought to have metabolic pathways and can influence host health [1, 2]. enhanced flavor and phenolic compound bioavailability Lactic acid bacteria (LAB) are present in fermented foods, through decreased contents of epigallocatechin gallate, such as vegetables (kimchi and sauerkraut) and dairy epigallocatechin, and epicatechin [3]. Tea fermented using products (yogurt and cheese); therefore, they are generally microorganism-derived enzymes has been investigated regarded as safe. Some LAB have probiotic characteristics, for digestibility, anticancer effects, and prevention and including maintenance of intestinal microflora, and treatment of cardiovascular disease [3-7]. antioxidant, anti-allergy, and anticancer properties, and The bioavailability of glucosides is increased by hydrolysis their use has increased with the goal of improving health of the sugar moiety using β-glucosidase [8]. The water or nutrition [1, 2]. Probiotic strains can be damaged by solubility and chemical stability of aglycone forms make exposure to simulated gastric conditions; however, some them effective for detoxifying endogenous metabolites and LAB isolated from fermented foods have a high survival xenobiotics, including defense against mycotoxins [4, 9]. rate under harsh conditions [1]. β-Glucosidase removes glucopyranosyl residues from the Traditional starter cultures used in the food industry are non-reducing end of β-glucoside by catalyzing the selected for their ability to rapidly produce desirable hydrolysis of the glycosidic bond [10]. β-Glucosidases are organoleptic qualities; however, probiotic bacteria should known to be widely distributed among animals, plants, May 2017 ⎪ Vol. 27⎪ No. 5 870 Lee and Paik fungi, yeasts, and bacteria [11]. As producer strains, [25]. Rh1 and Rh2 were reported to have anti-inflammatory β-glucosidases have been reported in L. acidophilus, effects [26, 27]. Rh2 produces anticancer [28, 29] and L. delbrueckii subsp. bulgaricus, L. casei, L. plantarum [12], antidiabetic effects by affecting the secretion of insulin [30, 31]. L. fermentum, and several Bifidobacterium sp. [5]. Most β- glucosidases can hydrolyze a broad range of substrates; Bioconversion of Ginsenosides by Enzymes and Microbial however, their huge diversity makes it difficult to predict Fermentation their aglycone specificity [13]. The production of the minor ginsenosides Rh1, Rh2, C-K, In this review, we summarize recent studies of Rg2, and F2 from major ginsenosides has been evaluated bioconversion of representative substances using LAB. previously (Fig. 1). Ginsenosides Rb1, Rb2, and Rc can be The roles of ginsenosides, γ-aminobutyric acid (GABA), transformed to C-K by human intestinal microorganisms hydroxytyrosol, isoflavones, and phenolic compounds in [32], and C-K has been shown to have anticancer effects in fermentation are considered. Additionally, the direction of tumor cell lines [33]. The efficacy of ginseng depends on future studies is discussed. the host’s intestinal condition, and therefore bioconversion is necessary for specific ginsenoside compounds. L. rossiae Bioconversion of Ginseng or Ginsenoside Using DC05, isolated using esculin-MRS agar, was used for LAB bioconversion of the major ginsenosides Rb1 and Re to C-K and Rg2 [34]. Leuconostoc mesenteroides LH1 isolated from Definition and Classification of Ginseng kimchi was used to produce β-glucosidase, and to convert Ginseng (Panax ginseng C.A. Mayer) is a well-known Rb1 to Rd, F2, and C-K [35]. The optimum conditions for medicinal plant in China, Korea, Japan, and other Asian conversion of Rb1 to C-K were pH 6.0, 30°C, and 72 h. countries [14, 15]. The major active ingredients of ginseng Several recombinant technologies have applied Bifidobacterium are ginsenosides, whose functions depend on the molecule strains to the production of ginsenoside aglycones [36, 37]. type [16-18]. Major ginsenosides have multiple sugar These bioconversion reactions are used to produce microbial moieties and are hardly absorbed by the human body [15]. crude enzymes whose mechanisms depend on the bacterial The major ginsenosides are glycosides that contain an strain. Lee et al. [38] reported changes in ginsenoside aglycone with tetracyclic triterpene, and include ginsenosides composition during fermentation of mixed cultures including Rb1, Rb2, Rc, and Rd, and protopanaxatriol-types such as Saccharomyces cerevisiae, L. acidophilus, L. plantarum, L. brevis, Re and Rg1, which comprise more than 90% of total and Bacillus subtilis. In addition, Jung et al. [39] conducted ginsenosides. Major ginsenosides can be converted into microbial fermentation of yogurt fortified with red ginseng deglycosylated ginsenosides and minor ginsenosides such extract. as F2, compound K (C-K), compound Mc, compound Y, Rg3, Rg2, Rh2, Rh1, and F1. Minor ginsenosides have more Bioconversion of Sodium Glutamate to effective pharmacological properties than major ginsenosides, γ-Polyglutamic Acid (γ-PGA) and GABA and can be bioconverted using heat, enzymes, and microorganisms. Characteristics, Function, and Synthesis of γ-PGA and GABA PGA has been used as an implantable biomaterial for Biofunctional Effects of Ginseng hydrogel formation because of its biodegradable, non- Ginseng has various biofunctional effects on liver, bone, toxic, and non-immunogenic properties [41, 42]. GABA is and brain health in humans. Ginsenosides Rb1, Rb2, and a nonprotein amino acid and the major inhibitory Rb3 influence liver health [19], the immune system [20], neurotransmitter of the central nervous system. GABA has and anti-inflammatory functions [18, 21], respectively. Rb1 antianxiety, antidepressant, and antihypertensive activities attenuated plasma aminotransferase activities and liver and regulates hormone secretion [43, 44]. GABA is widely inflammation to inhibit CCl4-induced liver fibrosis in rats [19]. distributed in mammals and plants, but its content under Rb2 prevented the lethal infection of the hemagglutinating natural conditions is low. Therefore, γ-PGA and GABA virus of Japan (HCJ) in mice [20]. Ginsenosides Rg1, Rg2, are produced by chemical synthesis or bioconversion and Rg3 are involved in bone health [22], neuroprotection methods developed using microorganisms [45-47]. Various [23], and vascular function modulation [24], respectively. microorganisms have been reported for GABA and γ-PGA In addition, mixtures of Rg1 and Rg2 improve cognitive production, including Bacillus sp., Escherichia coli, Aspergillus function through their effects on brain metabolic pathways sp., and LAB (Table 1) [43, 48, 49]. J. Microbiol. Biotechnol. Bioconversion Using Lactic Acid Bacteria 871 Fig. 1. Metabolic pathway of ginsenoside bioconversion using enzymes and microbial fermentation. B., Bifidobacterium; Leu., Leuconostoc; L., Lactobacillus; Rb1, 3-O-[β-D-glucopyranosyl-(1-2)-β-D-glucopyranosyl]-20-O-[β-D-glucopyranosyl-(1-6)-β-D- glucopyranosyl]-20(S)-protopanaxadiol; Rb2, 3-O-[β-D-glucopyranosyl-(1-2)-β-D-glucopyranosyl]-20-O-[α-L-arabinopyranosyl-(1-6)-β-D-glucopyranosyl]- 20(S)-protopanaxadiol; Rc, 3-O-[β-D-glucopyranosyl-(1-2)-β-D-glucopyranosyl]-20-O-[α-L-arabinofuranosyl-(1-6)-β-D-glucopyranosyl-]-20(S)-protopanaxadiol;