Bacteria on 2-keto-L-gulonic Acid Production: History
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Contributor:
Wenhu Chen
,
Qian Liu
,
Meng Liu
,
Hongling Liu
,
Di Huang
,
Yi Jiang
,
Tengfei Wang
,
Haibo Yuan

Vitamin C, a water-soluble vitamin with strong reducing power, cannot be synthesized by the human body and participates in a variety of important biochemical reactions. Vitamin C is widely used in the pharmaceutical, food, health care, beverage, cosmetics, and feed industries, with a huge market demand. The classical two-step fermentation method is the mainstream technology for vitamin C production. D-sorbitol is transformed into L-sorbose by Gluconobacter oxydans in the first step of fermentation; then, L-sorbose is transformed into 2-keto-L-gulonic acid (2-KGA) by a coculture system composed of Ketogulonicigenium vulgare and associated bacteria; and finally, 2-KGA is transformed into vitamin C through chemical transformation.

  • Vitamin C
  • 2-keto-L-gulonic acid
  • mixed fermentation

1. Introduction

Vitamin C, a water-soluble vitamin of vital importance to the human body, participates in many important biochemical reactions in organisms and contains an unsaturated enediol structure, thus having a strong reducing ability. In addition to its antioxidant function, vitamin C is involved in collagen synthesis, hormone synthesis, carnitine synthesis, gene transcription, regulation of translation, L-tyrosine catabolism, and iron absorption in humans [1]. As primates, guinea pigs, and fish lack gulonolactone oxidase (GULO), the enzyme required for vitamin C synthesis, they rely on exogenous vitamin C intake [2]. Vitamin C is widely used in the pharmaceutical, food, health, beverage, cosmetic, and feed industries [3] and has a huge market demand.
At present, vitamin C is primarily produced through the classical two-step fermentation process (Figure 1). Specifically, in the first step of fermentation, Gluconobacter oxydans converts D-sorbitol into L-sorbose, which is a fast and efficient process. By adding 300 g/L D-sorbitol in batch feeding, the yield of L-sorbose reaches 279.7 g/L at 16 h [4]. Then, in the second fermentation step, L-sorbose is converted into 2-keto-L-gulonic acid (2-KGA) through a coculture system composed of Ketogulonicigenium vulgare and associated bacteria. Subsequently, 2-KGA is converted to vitamin C by esterification and lactonization via chemical catalysis. Among these reactions, the transformation of L-sorbose to 2-KGA takes a long time, with a low yield and conversion rate (Table 1), so it is the committed step that determines the yield and cost of vitamin C.
Figure 1. The process of producing the vitamin C precursor 2-keto-L-gulonic acid by two-step fermentation.
Table 1. Fermentation yield of the coculture of K. vulgare and different associated bacteria.
Associated Bacteria Fermentation Container Time
(h)		 L-Sorbose Concentration (g/L) 2-KGA Concentration
(g/L)		 Conversion Rate
(%)		 References
Xanthomonas maltophilia IFO12692 3 L fermentor 60 126 124.0 - [5]
Bacillus cereus 112 Flask 45 85 63.4 - [6]
Bacillus megaterium 116 Flask 45 85 64.5 - [6]
Bacillus megaterium 116 and Bacillus cereus 112 (1:3, v/v) Flask 45 85 69.0 - [6]
Bacillus cereus HB601 Flask 96 80 - 93.0 [7]
Bacillus thuringiensis 320 260 m3 fermentor 48 88–92 90.2 94.5 [8]
Bacillus endophyticus Hbe603 Flask 72 - 70.0 93.0 [9]
Bacillus subtilis A9 Flask 48 92.5 71.2 - [10]
Bacillus cereus 112 Flask 55 110 98.5 89.5 [11]
Bacillus pumilus SH-B9 Flask 72 80 63.1 - [12]
Saccharomyces cerevisiae VTC2 Flask - 20 13.2 - [13]
Although the two-step fermentation method has advantages such as mature technology and high yield, it suffers from shortcomings such as high energy consumption, large equipment investment, and complex operation brought about by the two sterilization and fermentation steps. Therefore, extensive research has been conducted on one-step fermentation, and some researchers have achieved high 2-KGA yields with such an approach. For example, sorbose dehydrogenase (SDH) and sorbosone dehydrogenase (SNDH) of G. oxydans T100 were coexpressed in G. oxydans G624, which was a chemical mutation to inhibit the L-idonate pathway and the replacement of the original promoter with that of Escherichia coli tufB, resulting in a 2-KGA yield of 130 g/L from 150 g/L of D-sorbitol [14]. Wang et al. [15] deleted the gene involved in the L-sorbose metabolism of G. oxydans and cocultured G. oxydans with K. vulgare, obtaining a 2-KGA yield of 76.6 g/L within 36 h. Zhou et al. used the Gluconobacter oxydans ATCC9937 to direct the production of 2-KGA from D-glucose by balancing intracellular and extracellular D-glucose metabolic flux. The 2-KGA titer reached 30.5 g/L [16]. Despite some progress, the developed one-step fermentation method is not yet suitable for industrial production because of the low yield and low conversion rate.
The coculture process has been widely applied in wastewater treatment, biodegradation of textile azo dyes, treatment of contaminated soil, production of biofuels, and various bulk chemicals and natural products, with high application value [17]. Compared to monoculture, coculture systems can perform more complex tasks and have higher stability and robustness to environmental disturbances [17][18]. In addition, the coculture system can alleviate the growth damage or poor biosynthetic behavior of a single strain caused by excessive cell resource consumption and heavy metabolic burden through division of labor strategies [19]. The coculture system not only makes tasks that cannot be completed by a single strain possible, such as the coculture of Clostridium thermocellum to efficiently hydrolyze cellulose and Thermoanaerobacterium saccharolyticum to produce ethanol from sugars, which produced 38 g/L of ethanol from 92 g/L of avicel [20], but also improves yield and fermentation intensity, such as the coculture of associated bacteria with K. vulgare for 2-KGA production.
In the second step of the two-step fermentation method, K. vulgare, which is responsible for converting L-sorbose into 2-KGA, grows slowly and hardly produces 2-KGA when cultured alone [21][22]. However, when cocultured with associated bacteria that neither metabolize L-sorbose nor produce 2-KGA, K. vulgare can grow smoothly and efficiently to produce 2-KGA. A variety of associated bacteria, such as Xanthomonas maltophilia [5], Bacillus cereus, Bacillus megaterium [6], Bacillus thuringiensis [8], Bacillus endophyticus [9], Bacillus subtilis [10], Bacillus pumilus [12], and Saccharomyces cerevisiae [13], have previously been studied and exploited. Among them, B. megaterium is the most popular one for industrial production.
Stable interactions in microbial consortia generally rely on communication between cells through the coutilization of different substrates in the environment, the sequential conversion and reutilization of substrates, the complement of metabolites, and other ways to meet the normal growth of a single cell in a multicellular system [23]. However, in the second step of the two-step fermentation process for vitamin C production, what mechanism does the associated bacteria use to promote the growth of K. vulgare and the production of 2-KGA? This has always been a research hotspot, and researchers have conducted extensive research and in-depth exploration.

2. Effect of Associated Bacteria on the Growth and 2-KGA Production of K. vulgare

2.1. Fermentation Process

In the second step of the two-step fermentation method, K. vulgare and associated bacteria are usually prepared into mixed bacterial seeds through cocultivation and then inoculated into the fermentation medium [24]. It has been shown that the centrifugation supernatant and cytoplasmic matrix of B. megaterium can promote the growth of K. vulgare, and the presence of B. megaterium significantly shortens the lag time of K. vulgare [25]. At this stage, the associated bacteria grow rapidly, and the biomass of K. vulgare increases slowly, producing only a small amount of 2-KGA [24][26].
The coculture fermentation medium usually includes L-sorbose, corn steep liquor, urea, potassium dihydrogen phosphate, magnesium sulfate, and calcium carbonate [10][27]. Given that the associated bacteria cannot use L-sorbose, corn steep liquor is the only energy source for the associated bacteria, besides providing carbon sources, nitrogen sources, and growth factors. With the progress of fermentation, the nutrient components in the medium are rapidly consumed, leading to a lack of nutrition and especially energy. Poor nutritional conditions lead to the formation of spores by Bacillus [26][28]. Subsequently, Bacillus releases spores, which are accompanied by cell lysis, and the associated bacteria that cannot form spores undergo autolysis. As a result, peptides, proteins, purines, pyrimidines, and small molecules from the cytoplasm are released, which provides new nutrients for K. vulgare. From this moment on, K. vulgare enters the stage of rapid growth and rapid transformation of L-sorbose to 2-KGA [24].
The associated bacteria quickly absorb nutrients from the culture medium, except for L-sorbose, and synthesize the nutrients required for their own growth. Subsequently, the associated bacteria release new components and ratios of nutrients through secretion, release of spores, or cell lysis, which are utilized by K. vulgare. This phenomenon of sequential conversion and reutilization of substrates is common in cocultivation systems, such as the process of cellulose-to-ethanol transformation in the cocultivation of cellulose-decomposing microorganisms and ethanol-producing microorganisms [17]. Nutrients with new compositions and proportions are released by associated bacteria, stimulating the growth of K. vulgare and the production of 2-KGA.

2.2. Supplementation of Key Substance

Although K. vulgare has defects in amino acid, vitamin, coenzyme, and sulfur metabolism, it has a strong resource utilization and transportation system. In the GSMM of K. vulgare WSH-001, 103 genes were found responsible for the transport of exogenous polypeptides, and about 58 genes encoded aminopeptidases or peptidases that could hydrolyze polypeptides into amino acids [29]. Maximizing the use of nutrient elements in the environment is the way for many auxotrophic strains to survive in nature, and this is why associated bacteria can promote the growth and 2-KGA production of K. vulgare.
On the soft agar medium plate, the increase in amino acid concentration in the medium around K. vulgare colonies attracted B. megaterium to move and aggregate to K. vulgare; erythrose, erythritol, avian purines, and inositol were depleted by K. vulgare; and 2-KGA content in agar increased dramatically [28]. The same movement phenomenon was found when K. vulgare was cocultured with B. thuringiensis. Erythrose, erythritol, guanine, and inositol accumulated around B. thuringiensis were consumed by K. vulgare, and the production of 2-KGA increased sharply [30]. Additionally, B. megaterium WSH002 can secrete pantothenic acid and L-cysteine, which may be two potential growth promoters of K. vulgare because they are precursors of CoA [31]. Other studies have also shown that the adenine, guanine, and hypoxanthine required for K. vulgare in the middle stage of fermentation probably come from the decomposition of the associated bacteria [32].
In addition to the small-molecule metabolites, the associated bacteria also secrete proteins that can promote the growth and 2-KGA production of K. vulgare. B. megaterium secretes two different proteins, with molecular weights of 30–50 kDa and > 100 kDa, which can promote the growth of K. vulgare and increase the production of 2-KGA [33]. However, the specific protein and the mechanism by which it promotes K. vulgare growth and 2-KGA production have not yet been isolated and studied.
Reasonable utilization of material exchange between microorganisms can improve the biomass and product yield of coculture systems. For example, in the nitrogen- and fatty acid-limiting environment of water kefir, the presence of Saccharomyces cerevisiae improves the growth of Lactobacillus hordei by providing gluconate, fructose, amino acids, fatty acids, etc. [34]. Yeast utilizes oxygen respiration to produce carbon dioxide, while microalgae convert carbon dioxide into lipids and oxygen through photosynthesis [35]. Coculture of Rhodotorula glutinis and Scenedesmus obliquus in a photobioreactor increases the fermentation biomass by 40–50% and total lipids by 60–70%. [36]. However, in the continuous transformation and reutilization process of substrates, microorganisms that first utilize these substances will consume a portion for growth and metabolism; reducing these losses can improve the conversion efficiency of substrates. Similarly, in the coculture process of Bacillus and K. vulgare, a considerable part of the limited nutrients in the medium is locked in the spores. It has been shown that using lysozyme to lyse B. megaterium releases more intracellular substances than spore formation; the growth rate of K. vulgare increases by 27.4%, and the productivity of 2-KGA increases by 28.2%. [25]. Second, in the fermentation stage after the formation of spores, most of the nutrients for K. vulgare growth are provided by the lysate produced during the process of spore release by Bacillus, which leads to the problem that the substances released after spore decomposition may not completely meet the needs of K. vulgare. For example, in the coculture system with B. megaterium as associated bacteria, B. megaterium forms spores within 7–22 h, but the extracellular contents of L-proline, L-cysteine, L-valine, L-phenylalanine, and L-arginine remain 0 during 10–70 h of fermentation [37]. This indicates that these nutrients are leaked at low concentrations or that they are quickly absorbed and utilized by K. vulgare during spore release, and nutrients such as L-cysteine and L-proline, which cannot be synthesized by K. vulgare itself, may be factors limiting K. vulgare’s growth and 2-KGA production at this time.

2.3. Alleviation of Oxidative Pressure in Fermentation Systems

Autoxidation of flavin dehydrogenase [38][39] and non-respiratory flavoproteins in some metabolic pathways [40][41][42] can generate reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide, hydroxyl radicals, and nitric oxide. ROS are natural products of oxygen metabolism in aerobic organisms. Excessive levels of ROS in cells cause oxidative stress, which results in DNA damage, cell membrane peroxidation, inactivation of enzymes and cofactors, and eventually cell death [43]. The presence of cytochrome c in K. vulgare couples the production of 2-KGA with the respiratory chain [44], and ROS inhibits the growth of K. vulgare and the production of 2-KGA [45]. Except for the conversion process of L-sorbose to 2-KGA and other metabolic activities that produce a lot of ROS, 2-KGA as the target product also causes oxidative stress in K. vulgare [46][47].
To combat the ROS-induced damage to cells, biological organisms have developed a series of enzymes that can eliminate ROS, including superoxide dismutase, catalase, and peroxidase. The associated bacteria can induce the upregulation of these ROS-scavenging enzymes. For example, S. cerevisiae induces upregulation of superoxide dismutase, catalase, and oxidative stress–related genes (sod, cat, and gpd), thereby leading to increased 2-KGA production by K. vulgare [13]. Proteomic studies have shown that the enzymes in the microbial consortium that maintain the metabolic reduction environment of cells, including superoxide dismutase, glutathione S-transferase, NADPH: quinone oxidoreductase, and glucose-6-phosphate dehydrogenase, reach higher levels of expression during 18–23 h of fermentation [32].
Some small-molecular substances released by the associated bacteria may also help K. vulgare resist ROS. Proline can directly eliminate ROS and may also protect the stability of a variety of antioxidant enzymes [48]. L-cysteine can be used to synthesize GSH—the most important antioxidant in cells. Pyridoxine can quench ROS [49]. Vitamin C can alleviate oxidative stress in the environment and promote the growth and 2-KGA production of K. vulgare. Hence, using Saccharomyces cerevicae VTC2, which is genetically engineered to produce vitamin C from D-glucose, as an associated bacteria could increase 2-KGA production by 25% compared to the original strain [13]. Adenine, guanine, xanthine, and hypoxanthine produced by the associated bacteria may contribute to K. vulgare’s resistance to ROS [32]. Furthermore, the effect of B. megaterium–engineered bacteria that cannot form spores in the coculture system is weakened, which may be due to the absence or reduction of antioxidant substances called sporulenes, produced during the sporulation stage of B. megaterium [50][51].
Siderophores are secreted by microorganisms such as bacteria and fungi to obtain iron from the environment, and they can efficiently combine with low-molecular-weight substances of iron in the surrounding environment [52][53]. Most aerobic and facultative anaerobic microorganisms can synthesize at least one siderophore, and microorganisms growing under aerobic conditions require iron for a variety of functions, including the reduction of oxygen for ATP synthesis, the reduction of nucleoside precursors of DNA, heme formation, and other basic purposes [54]. It has been shown that K. vulgare cannot synthesize siderophores but has a siderophore-absorption system, and the addition of 500 µg/L Bacillus pumilus SY-A9 siderophores increases the titer of 2-KGA by 71.45% [12]. Further research has shown that siderophores cause overexpression of iron absorption system–related genes, electron transfer chain–related genes, ATP synthase–related genes, antioxidant enzyme–related genes, and 2-KGA production enzyme–related factors in K. vulgare 25B-1, thereby reducing oxidative stress and ensuring energy metabolism [12].
Despite the fact that the associated bacteria play a significant role in helping K. vulgare resist oxidation, the addition of antioxidant substances can further alleviate the oxidative stress of the fermentation system and improve the yield of 2-KGA. The addition of glutathione and oxidized glutathione with a concentration ratio of 50:1 in the fermentation system of B. endophyticus ST-1 as the associated bacteria increases the activities of total antioxidant capacity (t-AOC), total superoxide dismutase (T-SOD), and catalase (CAT) in the fermentation system and upregulates the expression of genes related to superoxide dismutase, such as sod, gst, gr, zwf, and gp, thereby eliminating oxidative stress, improving 2-KGA production, and shortening fermentation time [45]. Moreover, during the period when K. vulgare produces ROS due to the rapid dehydrogenation of L-sorbose to 2-KGA, the associated bacteria usually form spores or cell lysates. The antioxidant substances provided by associated bacteria lack a sustained supply during the high-speed production period of 2-KGA, so manual intervention to alleviate the oxidative pressure of K. vulgare in the later stage of fermentation may further improve the fermentation intensity.

This entry is adapted from the peer-reviewed paper 10.3390/fermentation9121000

References

  1. Doseděl, M.; Jirkovský, E.; Macáková, K.; Krčmová, L.K.; Javorská, L.; Pourová, J.; Mercolini, L.; Remião, F.; Nováková, L.; Mladěnka, P.; et al. Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination. Nutrients 2021, 13, 615.
  2. Valdés, F. Vitamin C. Actas Dermo-Sifiliogr. 2006, 97, 557–568.
  3. Yang, W.; Xu, H. Industrial Fermentation of Vitamin C. In Industrial Biotechnology of Vitamins, Biopigments, and Antioxidants; Vandamme, E., Revuelta, J.L., Eds.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2016; pp. 161–192.
  4. Giridhar, R.N.; Srivastava, A.K. Productivity improvement in L-sorbose biosynthesis by fedbatch cultivation of Gluconobacter oxydans. J. Biosci. Bioeng. 2002, 94, 34–38.
  5. Takagi, Y.; Sugisawa, T.; Hoshino, T. Continuous 2-Keto-l-gulonic acid fermentation by mixed culture of Ketogulonicigenium vulgare DSM 4025 and Bacillus megaterium or Xanthomonas maltophilia. Appl. Microbiol. Biotechnol. 2010, 86, 469–480.
  6. Mandlaa; Yang, W.C.; Han, L.T.; Wang, Z.Y.; Xu, H. Two-helper-strain co-culture system: A novel method for enhancement of 2-keto-L-gulonic acid production. Biotechnol. Lett. 2013, 35, 1853–1857.
  7. Zou, Y.; Hu, M.; Lv, Y.; Wang, Y.; Song, H.; Yuan, Y.J. Enhancement of 2-keto-gulonic acid yield by serial subcultivation of co-cultures of Bacillus cereus and Ketogulonicigenium vulgare. Bioresour. Technol. 2013, 132, 370–373.
  8. Yang, W.; Han, L.; Mandlaa, M.; Chen, H.; Jiang, M.; Zhang, Z.; Xu, H. Spaceflight-induced enhancement of 2-keto-L-gulonic acid production by a mixed culture of Ketogulonigenium vulgare and Bacillus thuringiensis. Lett. Appl. Microbiol. 2013, 57, 54–62.
  9. Jia, N.; Du, J.; Ding, M.Z.; Gao, F.; Yuan, Y.J. Genome Sequence of Bacillus endophyticus and Analysis of Its Companion Mechanism in the Ketogulonigenium vulgare-Bacillus Strain Consortium. PLoS ONE 2015, 10, 17.
  10. Yang, Y.; Gao, M.; Yu, X.D.; Zhang, Y.H.; Lyu, S.X. Optimization of medium composition for two-step fermentation of vitamin C based on artificial neural network-genetic algorithm techniques. Biotechnol. Biotechnol. Equip. 2015, 29, 1128–1134.
  11. Mandlaa; Sun, Z.Y.; Wang, R.G.; Han, X.D.; Xu, H.; Yang, W.C. Enhanced 2-keto-L-gulonic acid production by applying L-sorbose-tolerant helper strain in the co-culture system. AMB Express 2018, 8, 7.
  12. Zhang, Q.; Lin, Y.; Shen, G.; Zhang, H.; Lyu, S. Siderophores of Bacillus pumilus promote 2-keto-L-gulonic acid production in a vitamin C microbial fermentation system. J. Basic Microb. 2022, 62, 833–842.
  13. Wang, Y.; Li, H.C.; Liu, Y.; Zhou, M.Y.; Ding, M.Z.; Yuan, Y.J. Construction of synthetic microbial consortia for 2-keto-L-gulonic acid biosynthesis. Synth. Syst. Biotechnol. 2022, 7, 481–489.
  14. Saito, Y.; Ishii, Y.; Hayashi, H.; Imao, Y.; Akashi, T.; Yoshikawa, K.; Noguchi, Y.; Soeda, S.; Yoshida, M.; Niwa, M.; et al. Cloning of genes coding for L-sorbose and L-sorbosone dehydrogenases from Gluconobacter oxydans and microbial production of 2-keto-L-gulonate, a precursor of L-ascorbic acid, in a recombinant G. oxydans strain. Appl. Environ. Microbiol. 1997, 63, 454–460.
  15. Wang, E.X.; Ding, M.Z.; Ma, Q.; Dong, X.T.; Yuan, Y.J. Reorganization of a synthetic microbial consortium for one-step vitamin C fermentation. Microb. Cell. Fact. 2016, 15, 11.
  16. Li, G.; Li, D.; Zeng, W.; Qin, Z.; Chen, J.; Zhou, J. Efficient production of 2-keto-L-gulonic acid from D-glucose in Gluconobacter oxydans ATCC9937 by mining key enzyme and transporter. Bioresour. Technol. 2023, 384, 129316.
  17. Jiang, Y.; Wu, R.; Zhou, J.; He, A.; Xu, J.; Xin, F.; Zhang, W.; Ma, J.; Jiang, M.; Dong, W. Recent advances of biofuels and biochemicals production from sustainable resources using co-cultivation systems. Biotechnol. Biofuels. 2019, 12, 155.
  18. Brenner, K.; You, L.; Arnold, F.H. Engineering microbial consortia: A new frontier in synthetic biology. Trends Biotechnol. 2008, 26, 483–489.
  19. Agapakis, C.M.; Boyle, P.M.; Silver, P.A. Natural strategies for the spatial optimization of metabolism in synthetic biology. Nat. Chem. Biol. 2012, 8, 527–535.
  20. Argyros, D.A.; Tripathi, S.A.; Barrett, T.F.; Rogers, S.R.; Feinberg, L.F.; Olson, D.G.; Foden, J.M.; Miller, B.B.; Lynd, L.R.; Hogsett, D.A.; et al. High ethanol titers from cellulose by using metabolically engineered thermophilic, anaerobic microbes. Appl. Environ. Microbiol. 2011, 77, 8288–8294.
  21. Urbance, J.W.; Bratina, B.J.; Stoddard, S.F.; Schmidt, T.M.; Microbiology, E. Taxonomic characterization of Ketogulonigenium vulgare gen. nov., sp. nov. and Ketogulonigenium robustum sp. nov., which oxidize L-sorbose to 2-keto-L-gulonic acid. Int. J. Syst. Evol. Microbiol. 2001, 51, 1059–1070.
  22. Zou, W.; Liu, L.M.; Chen, J. Structure, mechanism and regulation of an artificial microbial ecosystem for vitamin C production. Crit. Rev. Microbiol. 2013, 39, 247–255.
  23. Ding, M.Z.; Song, H.; Wang, E.X.; Liu, Y.; Yuan, Y.J. Design and construction of synthetic microbial consortia in China. Synth. Syst. Biotechnol. 2016, 1, 230–235.
  24. Yang, W.C.; Sun, H.; Dong, D.; Ma, S.; Mandlaa; Wang, Z.X.; Xu, H. Enhanced 2-keto-L-gulonic acid production by a mixed culture of Ketogulonicigenium vulgare and Bacillus megaterium using three-stage temperature control strategy. Braz. J. Microbiol. 2021, 52, 257–265.
  25. Zhang, J.; Liu, J.; Shi, Z.P.; Liu, L.M.; Chen, J. Manipulation of B-megaterium growth for efficient 2-KLG production by K-vulgare. Process. Biochem. 2010, 45, 602–606.
  26. Wei, D.; Yuan, W.; Yin, G.; Yuan, Z.; Chen, M. Studies on kinetic model of vitamin C two-step fermentation process. Chin. J. Biotechnol. 1992, 8, 195–201.
  27. Zhang, Z.X.; Zhu, X.J.; Xie, P.; Sun, J.W.; Yuan, J.Q. Macrokinetic model for Gluconobacter oxydans in 2-keto-L-gulonic acid mixed culture. Biotechnol. Bioprocess Eng. 2012, 17, 1008–1017.
  28. Zhou, J.; Ma, Q.; Yi, H.; Wang, L.; Song, H.; Yuan, Y.J. Metabolome profiling reveals metabolic cooperation between Bacillus megaterium and Ketogulonicigenium vulgare during induced swarm motility. Appl. Environ. Microbiol. 2011, 77, 7023–7030.
  29. Zou, W.; Liu, L.M.; Zhang, J.; Yang, H.R.; Zhou, M.D.; Hua, Q.; Chen, J. Reconstruction and analysis of a genome-scale metabolic model of the vitamin C producing industrial strain Ketogulonicigenium vulgare WSH-001. J. Biotechnol. 2012, 161, 42–48.
  30. Jia, N.; Ding, M.Z.; Gao, F.; Yuan, Y.J. Comparative genomics analysis of the companion mechanisms of Bacillus thuringiensis Bc601 and Bacillus endophyticus Hbe603 in bacterial consortium. Sci. Rep. 2016, 6, 28794.
  31. Zou, W.; Zhou, M.D.; Liu, L.M.; Chen, J. Reconstruction and analysis of the industrial strain Bacillus megaterium WSH002 genome-scale in silico metabolic model. J. Biotechnol. 2013, 164, 503–509.
  32. Ma, Q.; Zhou, J.; Zhang, W.; Meng, X.; Sun, J.; Yuan, Y.J. Integrated proteomic and metabolomic analysis of an artificial microbial community for two-step production of vitamin C. PLoS ONE 2011, 6, e26108.
  33. Liu, L.M.; Chen, K.J.; Zhang, J.; Liu, J.; Chen, J. Gelatin enhances 2-keto-L-gulonic acid production based on Ketogulonigenium vulgare genome annotation. J. Biotechnol. 2011, 156, 182–187.
  34. Xu, D.; Behr, J.; Geißler, A.J.; Bechtner, J.; Ludwig, C.; Vogel, R.F. Label-free quantitative proteomic analysis reveals the lifestyle of Lactobacillus hordei in the presence of Sacchromyces cerevisiae. Int. J. Food Microbiol. 2019, 294, 18–26.
  35. Szotkowski, M.; Holub, J.; Šimanský, S.; Hubačová, K.; Sikorová, P.; Mariničová, V.; Němcová, A.; Márová, I. Bioreactor Co-Cultivation of High Lipid and Carotenoid Producing Yeast Rhodotorula kratochvilovae and Several Microalgae under Stress. Microorganisms 2021, 9, 1160.
  36. Yen, H.W.; Chen, P.W.; Chen, L.J. The synergistic effects for the co-cultivation of oleaginous yeast-Rhodotorula glutinis and microalgae-Scenedesmus obliquus on the biomass and total lipids accumulation. Bioresour. Technol. 2015, 184, 148–152.
  37. Li, Q.; Diao, J.; Xiang, B.T.; Cao, Z. Studies on metabolism of nitrogen source in fermentation of 2-keto-gulonic acid. Acta Microbiol. Sinica. 1996, 36, 19–24.
  38. Messner, K.R.; Imlay, J.A. The identification of primary sites of superoxide and hydrogen peroxide formation in the aerobic respiratory chain and sulfite reductase complex of Escherichia coli. J. Biol. Chem. 1999, 274, 10119–10128.
  39. Kussmaul, L.; Hirst, J. The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria. Proc. Natl. Acad. Sci. USA 2006, 103, 7607–7612.
  40. Massey, V.; Strickland, S.; Mayhew, S.G.; Howell, L.G.; Engel, P.C.; Matthews, R.G.; Schuman, M.; Sullivan, P.A. The production of superoxide anion radicals in the reaction of reduced flavins and flavoproteins with molecular oxygen. Biochem. Biophys. Res. Commun. 1969, 36, 891–897.
  41. Grinblat, L.; Sreider, C.M.; Stoppani, A.O. Superoxide anion production by lipoamide dehydrogenase redox-cycling: Effect of enzyme modifiers. Biochem. Int. 1991, 23, 83–92.
  42. Geary, L.E.; Meister, A. On the mechanism of glutamine-dependent reductive amination of alpha-ketoglutarate catalyzed by glutamate synthase. J. Biol. Chem. 1977, 252, 3501–3508.
  43. Farr, S.B.; Kogoma, T. Oxidative stress responses in Escherichia coli and Salmonella typhimurium. Microbiol. Rev. 1991, 55, 561–585.
  44. Wang, P.P.; Zeng, W.Z.; Du, G.C.; Zhou, J.W.; Chen, J. Systematic characterization of sorbose/sorbosone dehydrogenases and sorbosone dehydrogenases from Ketogulonicigenium vulgare WSH-001. J. Biotechnol. 2019, 301, 24–34.
  45. Huang, M.; Zhang, Y.H.; Yao, S.; Ma, D.; Yu, X.D.; Zhang, Q.; Lyu, S.X. Antioxidant effect of glutathione on promoting 2-keto-l-gulonic acid production in vitamin C fermentation system. J. Appl. Microbiol. 2018, 125, 1383–1395.
  46. Zhang, Q.; Lyu, S. 2-Keto-L-gulonic acid inhibits the growth of Bacillus pumilus and Ketogulonicigenium vulgare. World J. Microbiol. Biotechnol. 2023, 39, 257.
  47. Fang, J.; Wan, H.; Zeng, W.; Li, J.; Chen, J.; Zhou, J. Transcriptome Analysis of Gluconobacter oxydans WSH-003 Exposed to Elevated 2-Keto-L-Gulonic Acid Reveals the Responses to Osmotic and Oxidative Stress. Appl. Biochem. Biotechnol. 2021, 193, 128–141.
  48. Kaur, G.; Asthir, B.J.B.P. Proline: A key player in plant abiotic stress tolerance. Biol. Plant. 2015, 59, 609–619.
  49. Dalto, D.B.; Matte, J.J. Pyridoxine (Vitamin B6) and the Glutathione Peroxidase System; a Link between One-Carbon Metabolism and Antioxidation. Nutrients 2017, 9, 189.
  50. Zhu, Y.B.; Liu, J.; Du, G.C.; Zhou, J.W.; Chen, J. Sporulation and spore stability of Bacillus megaterium enhance Ketogulonigenium vulgare propagation and 2-keto-L-gulonic acid biosynthesis. Bioresour. Technol. 2012, 107, 399–404.
  51. Bosak, T.; Losick, R.M.; Pearson, A. A polycyclic terpenoid that alleviates oxidative stress. Proc. Natl. Acad. Sci. USA 2008, 105, 6725–6729.
  52. Kim, D.H.; Lee, D.; Monllor-Satoca, D.; Kim, K.; Lee, W.; Choi, W. Homogeneous photocatalytic Fe3+/Fe2+ redox cycle for simultaneous Cr(VI) reduction and organic pollutant oxidation: Roles of hydroxyl radical and degradation intermediates. J. Hazard. Mater. 2019, 372, 121–128.
  53. Górska, A.; Sloderbach, A.; Marszałł, M.P. Siderophore-drug complexes: Potential medicinal applications of the ‘Trojan horse’ strategy. Trends Pharmacol. Sci. 2014, 35, 442–449.
  54. Neilands, J.B. Siderophores: Structure and function of microbial iron transport compounds. J. Biol. Chem. 1995, 270, 26723–26726.
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