Elsevier

Biotechnology Advances

Volume 21, Issue 2, April 2003, Pages 109-122
Biotechnology Advances

Polysaccharopeptides of Coriolus versicolor: physiological activity, uses, and production

https://doi.org/10.1016/S0734-9750(03)00002-8Get rights and content

Abstract

The protein-bound polysaccharides or polysaccharopeptides produced by Coriolus versicolor are effective immunopotentiators, which are used to supplement the chemotherapy and radiotherapy of cancers and various infectious diseases. Antitumor activity of polysaccharopeptides has been documented. Several kinds of protein-bound polysaccharides have been shown to be produced by the white rot fungus, C. versicolor. Although some of these polymers are structurally distinct, they are not distinguishable in terms of their physiological activity. This review focuses on the physiologically active polysaccharopeptides of C. versicolor. In nature, C. versicolor occurs as a mushroom body, but the fungus can be grown as mycelial biomass in submerged culture in bioreactors. Mushrooms gathered in the wild, cultivated mushrooms, and the mycelial biomass of submerged culture are used to produce the polysaccharopeptides. Submerged cultures are typically carried out in batches lasting 5–7 days and at 25–27 °C. Hot water extraction of the biomass is used to recover the thermostable polysaccharopeptides that are concentrated, purified, and dried into a powder for medicinal use. In view of the documented physiological benefits of these compounds, extensive research is underway on the structure, composition, production methods, and use of new C. versicolor strains for producing the therapeutic biopolymers. Properties, physiological activity, recovery, and purification of the bioactive polysaccharopeptides are discussed.

Introduction

Medicinal mushrooms have an established history of use in traditional oriental therapies. Modern clinical practice in Japan, China, Korea, and other Asian countries continues to rely on mushroom-derived preparations. Medicinal effects have been demonstrated for many traditionally used mushrooms (Ooi and Liu, 1999), including extracts of Favolus alveolarius (Chang et al., 1988), Phellinus linteus Chung et al., 1993, Kim et al., 2001, Agaricus campestris (Gray and Flatt, 1998), Pestalotiopsis sp. (Kiho et al., 1997), Lentinus edodes Kim and Park, 1979, Sugano et al., 1985, Song et al., 1998, Pleurotus ostreatus (Kim and Park, 1979), Tricholoma sp. Wang et al., 1995, Wang et al., 1996a, Liu et al., 1996, and Coriolus versicolor Kim and Park, 1979, Mayer and Drews, 1980, Fujita et al., 1988, Li et al., 1990, Yang et al., 1992a, Han et al., 1996, Mao and Gridley, 1998, Ng, 1998, Ooi and Liu, 1999, Chu et al., 2002. Of the mushroom-derived therapeutics, polysaccharopeptides obtained from C. versicolor are commercially the best established. In addition to its medical applications, C. versicolor is widely used to degrade recalcitrant organic pollutants such as pentachlorophenol (PCP). Here we examine the properties, physiological activity, recovery, and purification of the bioactive polysaccharopeptides of C. versicolor.

Both extracellular and intracellular polysaccharopeptides of C. versicolor are physiologically active as biological response modifiers. In traditional medical practices of China and Japan, C. versicolor mushroom was harvested, dried, ground, and made into tea. Healing properties of C. versicolor extracts were noticed by Chinese and Japanese scientists and thus began an extensive controlled clinical research on C. versicolor extracts. Interestingly, the dose of the active polymers in the traditional tea was similar to that used in modern clinical practice. In nature, C. versicolor grows as a bracket or shelf mushroom; however, the fungus can be grown in submerged fermentation as mycelial biomass.

The best known commercial polysaccharopeptide preparations of C. versicolor are polysaccharopeptide Krestin (PSK) and polysaccharopeptide PSP. Both products are obtained from the extraction of C. versicolor mycelia. PSK and PSP are Japanese and Chinese products, respectively. Both products have similar physiological activities but are structurally different. PSK and PSP are produced from CM-101 and Cov-1 strains of C. versicolor, respectively. Both products are obtained by batch fermentation. PSK fermentation lasts up to 10 days, whereas PSP production involves a 64-h culture. PSK is recovered from hot water extracts of the biomass by salting out with ammonium sulfate, whereas PSP is recovered by alcoholic precipitation from the hot water extract.

PSK was commercialized by Kureha Chemicals, Japan. After extensive clinical trials, PSK was approved for use in Japan in 1977, and by 1985, it ranked 19th on the list of the world's most commercially successful drugs (Yang et al., 1992a). Annual Japanese sales of PSK in 1987 were worth US$357 million (Yang et al., 1992a). PSP appeared on the market about 10 years after PSK. In addition to clinically tested PSK and PSP, numerous other extract preparations of C. versicolor are on the market as neutraceuticals and traditional medicines. Neutraceutical polysaccharopeptide preparations are sold worldwide in the form of capsules, ground biomass tablets, syrups, food additives, and teas. Traditional usage, pharmacological activities, and clinical effects of C. versicolor preparations have been discussed by Chu et al. (2002).

Section snippets

C. versicolor mushroom

The visible form of C. versicolor is a fan-shaped mushroom with wavy margin and colored concentric zones (Fig. 1). C. versicolor is an obligate aerobe that is commonly found year-round on dead logs, stumps, tree trunks, and branches. The fungus occurs throughout the wooded temperate zones of Asia, Europe, and North America and may be the most common shelf fungus in the Northern Hemisphere. The mushroom belongs to the family Basidiomycotina.

Many different names have been used in the literature

Composition and physical properties of C. versicolor polysaccharopeptides

PSP and PSK are light or dark brown powders that are soluble and stable in hot water. The compounds are polysaccharopeptides Ueno et al., 1980a, Ueno et al., 1980b, Hotta et al., 1981 that are odorless and tasteless. The compounds do not have a definite melting point. Heating to more than about 120 °C gradually chars the polysaccharopeptides. The PSP/PSK polymers are soluble in water but insoluble in methanol, pyridine, chloroform, benzene, and hexane. An aqueous solution of PSP (1 g/100 ml

Physiological activity of polysaccharopeptides

An extremely broad range of physiological effects has been linked with the use of C. versicolor polysaccharopeptides. Some of the main effects include the following: immunopotentiation by inducing production of interleukin-6, interferons, immunoglobulin-G, macrophages, and T-lymphocytes; counter immunosuppressive effects of chemotherapy, radiotherapy, and blood transfusion; antagonization of immunosuppression induced by tumors; inhibition of proliferation of various cancers by inducing

Fermentation

C. versicolor polysaccharopeptides are commercially extracted from mushrooms or mycelia cultivated on solid substrates Yadav and Tripathi, 1991, Park et al., 1994 and mycelial biomass produced in submerged fermentations Yoshikumi et al., 1978a, Ueno et al., 1980a, Ueno et al., 1980b, Chen et al., 1981, Zhou et al., 1994, Cheng et al., 1998, Wang et al., 1996b. The major clinically approved polysaccharopeptide preparations PSK and PSP are obtained from submerged cultured mycelial biomass. In

Concluding remarks

The protein-bound polysaccharides of C. versicolor have been used as immunopotentiators and therapeutics for years. In view of the clearly documented physiological benefits of these compounds, extensive research is underway on the structure, composition, production methods, and use of new C. versicolor strains for producing the therapeutic biopolymers.

Physiologically active polysaccharopeptides can be produced from C. versicolor mushrooms harvested in the wild or cultivated commercially.

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