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Microbial cell as bio-factory for bioactive compounds: review on microbial nutraceuticals

Review Paper | March 1, 2019

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AllahNawaz Khan, Humaira Yasmin, Bin Amin, Liaqat Muhammad, Basharat Ullah Khan, Manzoor Ahmed

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Int. J. Biosci.14( 3), 207-220, March 2019

DOI: http://dx.doi.org/10.12692/ijb/14.3.207-220


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Now a days it is a challenging and very serious issue to meet an adequate supply of quality food for growing population which is exploding at a geometric progression. Nutrient deficient diet is one of the major cause of constantly increasing health related problems. To resolve the health issues caused by malnourishments, nutraceutical like polysaccharides, multi-vitamins and enzymes have been produced from plants since many years. However, use of plant-derived nutraceuticals is limited due to low growth rate, seasonal variation, plant diseases or other environmental influences. Instead, microorganisms can be used for rapid, ecofriendly and economically nutraceuticals production in less space and generation time.Scientists are focusing on cultivation of useful microbial strains that have the potential to produce metabolites possessing pharmaceutical as well as nutrition value (nutraceuticals). This modern approach can compensate for food demand (quality diets) and disease curing. Various bacteria, fungi, algae and yeast have been cultivated for the production of the bioactive compounds. Such useful microbial extracted compounds are considered to be food graded healthy nutrition or nutraceuticals. This advance research can bring revolution in the field of medicine and nutrition.


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Microbial cell as bio-factory for bioactive compounds: review on microbial nutraceuticals

Avula R, Kim SS, Chakrabarti S, Tyagi P,  Kohli N, Menon P. 2015. Delivering for Nutrition in Odisha: Insights from a Study on the State of Essential Nutrition Interventions. Poshan Report 7. New Delhi: International Food Policy Research Institute.

Annapurna V, Deosthale Y, Bamji M. 1991. Spirulina as a source of vitamin A. Plant Foods for Human Nutrition (formerly Qualitas Plantarum) 41, 125–34.

Applebaum D, Sabo DL, Fischer EH, Morris DR. 1975. Biodegradative ornithine decarboxylase of Escherichia coli. Purification, properties,andpyridoxal5’-phosphate binding site. Biochemical 14, 3675–3681.

Bajzer M, Seeley R. 2006. Physiology: obesity and gut flora. Nature 444, 1009–1010.

Barsh GS, Farooqi IS, O’Rahilly S. 2000. Genetics of body-weight regulation. Nature 404, 644–651.

Bercovici D, Fuller F. 1995. Industrial amino acids in nonruminant animal nutrition. In: Wallace, R.J., Chesson A (eds) Biotechnology in animal feeds and animal feeding, VCH, Weinheim, p 93–113.

Biesalski HK. 2001. Nutraceuticals: the link between nutrition and medicine. In: Kramer, K., Hoppe, P.P., Packer, L. (eds) Nutraceuticals in Health and Disease Prevention. Marcel Deckker, New York, p 1-26.

Belury MA. 2000. Dietary conjugated linoleic acid in health: physiological effects and mechanisms of action. Annual Review of Nutrition 22, 505–31.

Bergamo P, Luongo D, Miyamoto J, Cocca E, Kishino S, Ogawa J. 2014. Immunomodulatory activity of a gut microbial metabolite of dietary linoleic acid, 10-hydroxy-cis-12-octadecenoic acid, associated with improved antioxidant/detoxifying defences. Journal of Functional Foods 11, 192–202.

Bekers M, Upite D, Kaminska E, Laukevics J, Grube M, Vigants A, Linde R. 2005. Stability of levan produced by Zymomonas mobilis. Process Biochemistry 40, 1535–9.

Borowitzka L, Borowitzka M. 1989. β-Carotene (provitamin A) production with algae. Biotechnology of Vitamins, Pigments and Growth Factors. Vandamme, E.J., (ed.), Elsevier Applied Science. London, p 15–26.

Bower S, Perkins JB, Yocum RR, Howitt CL, Rahaim P, Pero J. 1996. Cloning, sequencing, and characterization of the Bacillus subtilis biotin biosynthetic operon. Journal of Bacteriology 178, 4122–30.

Bronzwaer S. 2008. EFSA scientific forum ‘from safe food to healthy diets’. EU risk assessment – Past, present and Future. Trends in Food Science and Technology 19, S2–S8.

Burja AM, Radianingtyas H, Windust A, Barrow CJ. 2006. ‘Isolation and characterisation of polyunsaturated fatty acid producing Thraustochytrium species; screening of strains and optimization of omega-3 production’. Appllied Microbiology and Biotechnology 72, 1161–9.

Cai L, Yuan MQ, Li ZJ, Chen JC, Chen GQ. 2012.  Genetic engineering of Ketogulonigenium vulgare for enhanced production of 2-keto-L-gulonic acid. Journal of Biotechnology 157, 320–5.

Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, Muccioli GG, Delzenne NM. 2009. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 58, 1091–1103.

Chibata I, Kakimoto T, Kato J. 1965. Enzymatic production of l-alanine by Pseudomonas dacunhae. Applied Microbiology 13, 638–45.

Clugston GA, Smith TE. 2002. Global nutrition problems and novel foods. Asia Pacific Journal of Clinical Nutrition. 11(s6).

Combie J. 2006. Properties of levan and potential medical uses, in polysaccharides for drug delivery and pharmaceutical applications, ACS Symposium Series. Journal of the American Chemical Society 934, 263–9.

Casterton PL, Curry LL, Lina BAR, Wolterbeek APM, Kruger CL. 2009. 90-Day feeding and genotoxicity studies on a refi ned arachidonic acid-rich oil. Food and Chemical Toxicology 47, 2407–18.

Craciun S, Marks JA, Balskus EP. 2014. Characterization of choline trimethylaminelyase expands the chemistry of glycyl radical enzymes. ACS Chemical Biology 9, 1408–13.

Dawson LF, Donahue EH, Cartman ST, Barton RH, Bundy J, McNerney R, Minton NP, Wren BW. 2011. The analysis of para-cresol production and tolerance in Clostridium difficile 027 and 012 strains. BMC microbiology 11, 86.

Den Besten G, Van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. 2013. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. Journal of Lipid Research 54, 2325–40.

D ’Donnell K. 2006. Aspartame and neotame. In: sweeteners and augar alternatives in food technology. Mitchell, H.L. (ed). Blackwell Publishing, Oxford, p 86–102.

Dmytruk KV, Yatsyshyn VY, Sybirna NO, Fedorovych DV, Sibirny AA. 2011. Metabolic engineering and classic selection of the yeast Candida famata (Candida flareri) for construction of strains with enhanced riboflavin production. Metabolic Engineering 13, 82–8.

Dufosse L. 2009. Pigments. Microbial Encyclopedia Microbiology 4, 457–471.

Duncan SH, Barcenilla A, Stewart CS, Pryde SE, Flint HJ. 2002.  Acetate utilization and butyryl coenzyme A (CoA):acetate-CoA transferase in butyrateproducing bacteria from the human large intestine. Applied and Environmental Microbiology. 68, 5186–90.

Eggersdorfer M, Adam G, John MWH, Labler L. 1996. Vitamins. Biotechnology 4, Pape, H., Rehm, H.J. (eds). VCH, Weinheim, p  114–58.

El Shafey HM, Ghanem S, Guyonvarch A. 2009. Cloning of recA gene of Corynebacterium glutamicum and phenotypic complementation of Escherichia coli recombinant deficient strain. World Journal of Microbiology and Biotechnology 25, 367–373.

Furuichi K, Hojo K, Katakura Y, Ninomiya K, Shioya S. 2006. Aerobic culture of Propionibacterium freudenreichii ET-3 can increase production ratio of 1,4-dihydroxy-2-naphthoic acid to menaquinone. Journal of Bioscience and Bioengineering 101, 464–70.

Giavasis I, Biliaderis C. 2006. Microbial polysaccharides, in functional food carbohydrates, Biliaderis ,C., Izydorczyk, M. (eds). CRC Press, New York, p  167–214.

Goese MG, Perkins P, Sehyns G. 2006.  Thiamin Production by Fermentation.US Patent Pub No US2006/0127993 A1.

Goodridge HS, Wolf, AJ, Underhill DM. 2006. β-glucan recognition by the innate immune system. Immunological Reviews 230, 38–50.

Gupta P, Andrew H, Kirschner BS, Guandalini S. 2000. Is Lactobacillus GG Helpful in Children with Crohn’s Disease? Results of a Preliminary, Open-Label Study. Journal of Pediatric Gastroenterology and Nutrition 31, 453–457.

Hardy G. 2000. Nutraceuticals and functional foods: Introduction and meaning. Nutrition 16, 688–9.

Han YW. 1990. Microbial levan. Advances in Applied Microbiology 35, 171–94.

He JZ, Ru QM, Dong DD, Sun PL. 2012. Chemical characteristics and antioxidant properties of crude water soluble polysaccharides from four common edible mushrooms. Molecules 17, 4373–87.

He X, Guo X, Liu N, Zhang B. 2007. Ergosterol production from molasses by genetically modified Saccharomyces cerevisiae. Applied Microbiology and Biotechnology 75, 55–60.

Hugenholtz J, Smid EJ. 2002. Nutraceutical production with food-grade microorganisms. Current Opinion in Biotechnology 13, 497–507.

Kang SA, Hong K, Jang KH, Kim S, Lee KH, Chang BI, Kim CH, Choue R. 2004. Antiobesity and hypolipidemic effects of dietary levan in high fat diet-induced obese rats. Journal of Microbiology and Biotechnology 14, 796–804.

Kassinen A, Krogius-Kurikka L., Makivuokko H, Rinttila T, Paulin L, Corander J, Malinen E, Apajalahti J, Palva  A. 2007. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology 133, 24–33.

Kato T, Park EY. 2012.  Riboflavin production by Ashbya gossypii. Biotechnology Letters 4, 611–18.

Kinoshita S, Udaka S, Shimono M. 1957a. Studies on the amino acid fermentation. Part 1. Production of L-glutamic acid by various microoganism. Journal of General and Applied Microbiology 3, 193–205.

Kinoshita S, Nakayama K, Udaka S. 1957b. The fermentative production of L-ornithine (preliminary report). Journal of General and Applied Microbiology. 3, 276–7.

Kim J, Park W. 2013.  Indole inhibits bacterial quorum sensing signal transmission by interfering with quorum sensing regulator folding. Microbiology. 159, 2616–25.

Kumagai H, Hatsui H, Yamada H. 1970. Formation of tyrosine phenol-lyase by bacteria. Agricaltural and Biological Chemistry 34, 1259–61.

Kumagai H, Kashima N, Torii H, Yamada H, Enei H, Okumura S. 1972. Purification, crystallization and properties of tyrosine phenol lyase from Erwinia herbicola. Agricaltural and Biological Chemistry 36, 472–82.

Kurbanoğlu EB, 2001. Production of single-cell protein from ram horn hydrolyzate. Turkish Jouranl ofBiology 25, 371–377.

Lamberti C, Purrotti M, Mazzoli R, Fattori P, Barello C, Coïsson JD. 2011. ADI pathway and histidine decarboxylation are reciprocally regulated in Lactobacillus hilgardii ISE 5211: proteomicevidence. Amino Acids 41, 517–527.

Leathers TD. 2002. Dextran in biopolymers, Vol 5. Polysaccharides I:Polysaccharides from Procaryotes, Vandamme, E.J., De Baets, S., Steinbuechel, A. (eds). Wiley-VCH, Weinheim, p 299–321.

Lipton M. 2001. Challenges to meet: Food and nutrition security in the new millennium. Proceedings of  the Nutrition Society 60, 203–214.

Mashaghi S, Jadidi T, Koenderink G, Mashaghi A. 2013. “Lipid nanotechnology”. International  Journal of Molecular Sciences 14, 4242–82.

Misak A. 2004. Elsinan, an extracellular α-1,3 : 1,4 glucan produced by Elsinoe leucospila: Production, structure, properties and potential food utilization. Foods and food ingredients journal of Japan 209, 286–97.

Miyata R, Yonehara T. 1999. Method for Producing Folic Acid. US Patent 5, 968-788.

Mizuno T. 2002. Medicinal properties and clinical effects of culimary-medicinal mushroom Agaricus blazei Murill (Agaricomycetidae). International Journal of Medicinal Mushrooms 4, 4.

Mizuno T, Hagiwara T, Nakamura T, Ito H, Shimura K, Sumiy T, Asakura A. 1990. Antitumor activity and some properties of water-soluble polysaccharides from ‘Himematsutake’, the fruiting body of Agaricus blazei Murrill. Agricaltural and Biological Chemistry 54, 2889–96.

Moriya T, Hikichi Y, Moriya Y, Yamaguchi T. 1999. Takeda Chemical Industries, Ltd.,  Process for producing D-pantoic acid and D-pantothenic acid or salts thereof. U.S. Patent 5, 932.

Nagasawa T, Yamada H. 1989. Microbial transformations of nitriles. Trends in Biotechnology. 7, 153–158.

Nakayama R, Kumagai H, Maruyama T, Tochikura T, Ueno T, Fukami H. 1981. Synthesis of γ-glutamylpeptides by γ-glutamylcysteine synthetase from Proteus mirabilis. Agricaltural and Biological Chemistry 45, 2839–2845.

Nelis H, de Leenheer A. 1991.  Microbial sources of carotenoid pigments used in foods and feeds. Jouranlof Applied Bacteriology 70, 181–191.

Nagy K, Tiuca ID. 2017.  Importance of Fatty Acids in Physiopathology of Human Body. In Fatty Acids. InTech.

Notararigo S, Nácher-vázquez M, Ibarburu I, Werning ML, De palencia PF, Duenasmt Aznar R, López P, Prieto A. 2012. Comparative analysis of production and purification of homo- and hetero-polysaccharides produced by lactic acid bacteria. Carbohydartes Polymers 93, 57-64.

Osawa T. 2007. Nephroprotective and hepatoprotective effects of curcuminoids. Advances in Experimental Medicine and Biology 595, 407–423.

Ohno N, Miura T, Miura NN, Adachi Y. Yadomae T. 2001. Structure and biological activities of hypochlorite oxidized zymosan. Carbohydrates Polymers 44, 339–49.

Ohshiro T, Yamamoto M, Izumi Y, Bui BT, Florentin D, Marquet A. 1994. Enzymatic conversion of dethiobiotin to biotin in cell-free extracts of a Bacillus sphaericus bioB transformant. Bioscience, Biotechnology, and Biochemistry 58, 1738–41.

Porto B, Mangiapane E, Pessione A, Neves MJ,  Pessione E, Martins FS. 2015. The effects of sodiums elenite on the probiotic Saccharomyces cerevisiae UFMG A-905:A physiological and proteomic analysis. Journal of Functional Foods 17, 828–836.

Pulz O, Gross W. 2004. Valuable products from biotechnology of microalgae. Applied Microbiology and Biotechnology 65, 635–48.

Ratledge C. 2005.  Microbial production of gamma-linolenic acid. In Handbook of Functional Lipids. Akoh, A.A. (ed). Baco Raton, Taylor & Francis, p 19–45.

Reichardt N, Duncan SH, Young P, Belenguer, A, McWilliam Leitch C, Scott K. 2014.  Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME Journal 8, 1323–35.

Ruas-Madiedo P, Hugenholtz J, Zoon P. 2002. An overview of the functionality of exopolysaccharides produced by lactic acid bacteria. International Dairy Journal 12, 163–71.

Running JA, Huss RJ, Olson PT. 1994. Heterotrophic production of ascorbic acid by microalgae. Journal of Applied Phycology 6, 99–104.

Sousa R, Halper J, Zhang J, Lewis SJ, Li W. 2008. Effect of Lactobacillus acidophilus supernatants on body weight and leptin expression in rats. BMC Complementary and Alternaive Medicine. 8, 5–12.

Sabra W, Zeng AP, Deckwer WD. 2001. Bacterial alginate: physiology, product quality and process aspects. Applied Microbiology and Biotechnology 56, 315–25.

Sahm H, Eggeling L. 1999.  d-pantothenate synthesis in Corynebacterium glutamicum and use of panBC and genes encoding L-valine synthesis for d-pantothenate overproduction. Applied and Environmental Microbiology 55, 1973–9.

Sanyal I, Gibson KJ, Flint DH. 1996. Escherichia coli biotin synthase: An investigation into the factors required for its activity and its sulfur donor. Archives of Biochemistry and Biophysics 326, 48–56.

Sato T, Tosa T. 1993. Production of L-aspartic acid. Bioprocess Technology 16, 15–24.

Sato T, Yamada Y, Ohtani Y, Mitsui N, Murasawa H, Araki S. 2001.  Efficient production of menaquinone (vitamin K2) by a menadione-resistant mutant of Bacillus subtilis.Journal of Industrial Microbiology and Biotechnology 26, 115–20.

Shirasug N, Misaki A. 1992. Isolation, characterization, and antitumor activities of the wall polysaccharides from Elsinoe leucospila. Bioscience, Biotechnology, and Biochemistry 56, 29–33.

Shibasaki T, Mori H, Ozaki A. 2000. Enzymatic production of trans-4-hydroxyl-proline by regio- and stereospecifi c hydroxylation of L-proline. Bioscience, Biotechnology, and Biochemistry 64, 746–50.

Shimizu S. 2008. Vitamins and related compounds: microbial production. Biotechnology: Special Processes, Volume 10, 2nd edition, Rehm,H.J. and Reed, G. (eds). Wiley-VCH, Weinheim, Germany.

Stahmann KP, Revuelta JL, Seulberger H. 2000. Three biotechnical processes using Ashbya gossypii, Candida famata or Bacillus subtilis compete with chemical riboflavin production. Applied Microbiology and Biotechnology 53, 509–516.

Suzuki H, Kato K, Kumagai H. 2004. Development of an efficient enzymatic production of γ-d-glutamyl-l-tryptophan (SCV-07), a prospective medicine for tuberculosis, with bacterial γ-glutamyltranspeptidase. Journal of Biotechnology. 111, 291–5.

Tani Y. 1989.  Microbial production of vitamin B6 derivatives. Biotechnology of Vitamins, Pigments and Growth Factors, Vandamme, E.J. (ed.). Elsevier Applied Science London, p 221–30.

Thauer RK, Moller-Zinkhan D, Spormann AM. 1989. Biochemistry of acetate catabolism in anaerobic chemotrophic bacteria. Annual Review of Microbiology 43, 43–67.

UNICEF. 2016. Global nutrition report. data.unicef.org/resources/2016-global-nutrition report.

Valentin HE, Qi Q. 2005.  Biotechnological production and application of vitamin E: Current state and prospects. Applied Microbiology and Biotechnology 68, 436–44.

Visick KL, Fuqua C. 2005. Decoding microbial chatter:cell-cell communication in bacteria.Journal of Bacteriology 187, 5507–5519.

Watanabe F. 2007.  Vitamin B12 sources and bioavailability. Experimental Biology and Medicine. 232:1266–74.

Wojcikowski K, Johnson DW, Gobe GC. 2006. Herbs or natural substances as complementary therapies for chronic kidney disease: ideas for future studies. Journal of Laboratory and Clinical Medicine. 147, 160–166.

Wen, Z.Y, Chen F. 2003. Heterotrophic production of eicosapentaenoic acid by microalgae.Biotechnology Advances 21, 273–94.

Yamada H, Takahashi S, Kii Y, Kumagai H. 1978. Distribution of hydantoin hydrolyzing activity in microorganisms. Journal of Fermentation Technology 56, 484–91.

Yamamoto S, Wakayama M, Tachiki T. 2005. Theanine production by coupled fermentation with energy transfer employing Pseudomonas taetrolens Y-30 glutamine synthetase and baker’s yeast cells. Bioscience, Biotechnology, and Biochemistry 69, 784–9.

Yang B, Chen H, Gu Z, Tian F, Ross RP, Stanton. 2014. Synthesis of conjugated linoleic acid by the linoleate isomerase complex in foodderived lactobacilli.  Journal of Applied Microbiology. 117, 430–9.

Yasuda T, Ueda J, Ohsawa K. 2001. Urinary metabolites of genistein administered orally to rats. Chemical and Pharmaceutical Bulletin 49, 1495–7.

Ye VM, Bhatia SK. 2012. Pathway engineering strategies for production of beneficial carotenoids in microbial hosts. Biotechnology Letters 34, 1405–14.

Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D, Weinberger. 2015.  Personalized nutrition by prediction of glycemic responses. Cell. 163, 1079–94.

Zhan XB, Lin CC, Zhang HT. 2012. Recent advances in curdlan biosynthesis, biotechnological production, and applications.Applied Microbiology and Biotechnology 93, 525–31.

Zhu T, Pan Z, Domagalski N, Koepsel R, Ataai, MM, Domach MM. 2005.  Engineering of Bacillus subtilis for enhanced total synthesis of folic acid. Applied and Environmental Microbiology 71, 7122–9.