Natural products from endophytic microbes have been observed to inhibit or kill a wide variety of harmful disease-causing agents, including, but not limited to, phytopathogens, as well as bacteria ,fungi, viruses and protozoan that affect humans and animals. Cryptosporiopis Quercia, a fungus commonly associated with hardwood species in Europe, has been isolated as an endophyte from Tripterigeum wilfordii, a medicinal plant native to Eurasia. On Petri plates, C.quercina demonstrates excellent anti fungal activity against some important human fungal pathogens - Candida albicans and Trichophyton sp. Since infections caused by fungi are a growing health problem, especially amongst AIDS patients, and those who are otherwise immunocompromised, new antimycotics are needed to combat this problem. A unique peptide antimycotics, termed crypto candin, has been isolated and characterized from C. quercina. This compound contains a number of hydroxylated amino acids and a novel amino acid (3-hydroxy-4-hydroxy methyl proline). The bio active compound is related to known antimycotics , such as the rchinocandins and the pneumocandins. Cryptocandin is also active against a number of plant parthogenic fungi, including Sclerotinia sclerotiorum and Botrytis cinerea ,and is currently being tested and developed by several companies for use against a number of fungi causing diseases of skin and nails.
Sttins
The so-called statins are a group of compounds which act as potent competitive inhibitors of 3-HMG-CoA-redux taste, a key enzyme in the biosynthesis of cholesterol. These organic acids interact with the enzyme through their acidic side groups and in doing is effect a reduction in plasma cholesterol levels. The most important statins commercially are them evinced acids, with the most notable being lovastatin from Monascus river and mevastatin from Penicillium citrin in.Both mevastatin and lovastatin can be converted into the compounds ML-236A and monacolin J respectively by chemical means or by microbial transformation Each of these compounds differs in their affinity for 3-HMG-CoA-redux taste and,thus, in their effectiveness. Research and development over the last two decades has shown that a number of fungi produce a range of similar compounds with cholesterol-lowering effects. One interesting aspect of their commercial production lies in the ability to produce these compounds by liquid fermentation ( e.g.lovastation from Aspergillus terreus) or by using solid-state fermentation , the so-called Koji process ( e.g. Lovastotion from Monascus rubber).
Cyclosporin A
Immunosuppressive drugs have transformed modern transplant surgery by vastly reducing the incidence of organ rejection. The discovery and exploitation of the powerful immunosuppressant cyclosporin A has relied almost completely on fungal biotechnology . Attempts at chemically synthesizing the drug have served to illustrate the complexity of fungal secondary metabolism. Cyclosporin A is produced dy the fungus Tolypocladium inflatum and was initially isolated from a Norwegian soil sample. The compound inhibits the prodoction of interleukin 2 by T-lymphocytes and in so doing inhibits any potential immune response stimulated by antigens produced against transplanted organs. Cyclosporin A has also found use in the treatment of medical conditions such as psoriasis and eczema, owing to the role of interleukin-2in mediating inflammatory responses.
The structure of cyclosporine A has shown it to be a heavily methylated cyclic peptide . In a similar fashion to other secondary metabolites, a range of over 25 cyclosporin analogues is produced by T.inflatum, and while 17 have anti fungal activity, only two are immunosuppressants. Following a series of strain improvements using mutagenesis and culture optimization, gram-quantity yields per liter have been achieved under optimized fermentation conditions. Despite the best efforts at chemical synthesis of the drug, production of cyclosporine A is still. Only economically feasible by natural means.
Pharmacologically active products
In addition to antibiotics, fungi, as illustrated in Table 6.2, produce a range of other secondary metabolites. Some of these compounds are very significant in terms of their medical importance, including cyclosporin A and a group of compounds with cholesterol-lowering properties known as the statins. Other compounds, which will be discussed, include the alkaloids and the gibberellins.
ฟิต222.docx
Alkaloids
Members of the genus Claviceps a parasitic fungus which grows on a wide variety of grains synthesize numerous secondary metabolites known as alkaloids.
These compounds are produced in the sclerotic do the fungus, the resting structure with which the fungus ensures its survival over winter. Many of these alkaloids are pharmaceutically important and can act in a variety of ways, but they particularly affect the central nervous system, causing hallucinations or convulsions. Thanks common core of these compounds is the tetracyclic alkaloid ring structure(ergoline nucleus) in which the nitrogen atom at position 6 is usually unregulated. This core structure is derived from tryptophan and mevalonic acid and can be modified with varying degrees of complexity to give rise to a multitude of alkaloids, each differing in their potency and toxicity. These derivatives can then be used in the chemical synthesis of additional pharmacologically active compounds. For instance, lysergic acid diethylamide (LSD) is sympathetically derived from lysergic acid, an alkaloid by Claviceps paspali. Medically speaking, many of these alkaloids are important owing to their negative effect;indeed, alkaloid-contaminated bread caused numerous outbreaks of ergotism until the eighteenth century. There is also evidence to suggest that the Salem Witch trials were brought about following outbreaks of ergotism.
Medically useful alkaloids have, however, been isolated, and the most useful of these are the alkaloids ergometrine and it's methylated derivative methyl etgometrine. Both of these compounds stimulate contractionin of uterine smooth muscle and can also be used as vasoconstrictors to control excessive bleeding after childbirth
6.4.4 Gibberellins
The gibberellins are a group of diterpenoid compounds containing 19 or 20 carbon atoms and are capable of promoting numerous developmental include the induction of bolting, production of hydrologic enzymes and stimulation of both cell elongation and cell division. These secondary metabolites are biosynthesized form mevelonic acid by Gibberella fujikora, though they have also been isolated from Sphacaloma nonprofits, Neurospora crassa, Rhizobium bordello and Azospirillium lipoferrum. They have numerous agricultural applications, including their use in malting, fruit ripening and improving fruit set and size . On an industrial scale, the most important production organism is G. families, from which mutated strains secrete gibberellins at gram per litre quantities.
Natural products from endophytic microbes have been observed to inhibit or kill a wide variety of harmful disease-causing agents, including, but not limited to, phytopathogens, as well as bacteria ,fungi, viruses and protozoan that affect humans and animals. Cryptosporiopis Quercia, a fungus commonly associated with hardwood species in Europe, has been isolated as an endophyte from Tripterigeum wilfordii, a medicinal plant native to Eurasia. On Petri plates, C.quercina demonstrates excellent anti fungal activity against some important human fungal pathogens - Candida albicans and Trichophyton sp. Since infections caused by fungi are a growing health problem, especially amongst AIDS patients, and those who are otherwise immunocompromised, new antimycotics are needed to combat this problem. A unique peptide antimycotics, termed crypto candin, has been isolated and characterized from C. quercina. This compound contains a number of hydroxylated amino acids and a novel amino acid (3-hydroxy-4-hydroxy methyl proline). The bio active compound is related to known antimycotics , such as the rchinocandins and the pneumocandins. Cryptocandin is also active against a number of plant parthogenic fungi, including Sclerotinia sclerotiorum and Botrytis cinerea ,and is currently being tested and developed by several companies for use against a number of fungi causing diseases of skin and nails.SttinsThe so-called statins are a group of compounds which act as potent competitive inhibitors of 3-HMG-CoA-redux taste, a key enzyme in the biosynthesis of cholesterol. These organic acids interact with the enzyme through their acidic side groups and in doing is effect a reduction in plasma cholesterol levels. The most important statins commercially are them evinced acids, with the most notable being lovastatin from Monascus river and mevastatin from Penicillium citrin in.Both mevastatin and lovastatin can be converted into the compounds ML-236A and monacolin J respectively by chemical means or by microbial transformation Each of these compounds differs in their affinity for 3-HMG-CoA-redux taste and,thus, in their effectiveness. Research and development over the last two decades has shown that a number of fungi produce a range of similar compounds with cholesterol-lowering effects. One interesting aspect of their commercial production lies in the ability to produce these compounds by liquid fermentation ( e.g.lovastation from Aspergillus terreus) or by using solid-state fermentation , the so-called Koji process ( e.g. Lovastotion from Monascus rubber).Cyclosporin AImmunosuppressive drugs have transformed modern transplant surgery by vastly reducing the incidence of organ rejection. The discovery and exploitation of the powerful immunosuppressant cyclosporin A has relied almost completely on fungal biotechnology . Attempts at chemically synthesizing the drug have served to illustrate the complexity of fungal secondary metabolism. Cyclosporin A is produced dy the fungus Tolypocladium inflatum and was initially isolated from a Norwegian soil sample. The compound inhibits the prodoction of interleukin 2 by T-lymphocytes and in so doing inhibits any potential immune response stimulated by antigens produced against transplanted organs. Cyclosporin A has also found use in the treatment of medical conditions such as psoriasis and eczema, owing to the role of interleukin-2in mediating inflammatory responses. The structure of cyclosporine A has shown it to be a heavily methylated cyclic peptide . In a similar fashion to other secondary metabolites, a range of over 25 cyclosporin analogues is produced by T.inflatum, and while 17 have anti fungal activity, only two are immunosuppressants. Following a series of strain improvements using mutagenesis and culture optimization, gram-quantity yields per liter have been achieved under optimized fermentation conditions. Despite the best efforts at chemical synthesis of the drug, production of cyclosporine A is still. Only economically feasible by natural means.Pharmacologically active productsIn addition to antibiotics, fungi, as illustrated in Table 6.2, produce a range of other secondary metabolites. Some of these compounds are very significant in terms of their medical importance, including cyclosporin A and a group of compounds with cholesterol-lowering properties known as the statins. Other compounds, which will be discussed, include the alkaloids and the gibberellins.ฟิต222.docxAlkaloidsMembers of the genus Claviceps a parasitic fungus which grows on a wide variety of grains synthesize numerous secondary metabolites known as alkaloids.These compounds are produced in the sclerotic do the fungus, the resting structure with which the fungus ensures its survival over winter. Many of these alkaloids are pharmaceutically important and can act in a variety of ways, but they particularly affect the central nervous system, causing hallucinations or convulsions. Thanks common core of these compounds is the tetracyclic alkaloid ring structure(ergoline nucleus) in which the nitrogen atom at position 6 is usually unregulated. This core structure is derived from tryptophan and mevalonic acid and can be modified with varying degrees of complexity to give rise to a multitude of alkaloids, each differing in their potency and toxicity. These derivatives can then be used in the chemical synthesis of additional pharmacologically active compounds. For instance, lysergic acid diethylamide (LSD) is sympathetically derived from lysergic acid, an alkaloid by Claviceps paspali. Medically speaking, many of these alkaloids are important owing to their negative effect;indeed, alkaloid-contaminated bread caused numerous outbreaks of ergotism until the eighteenth century. There is also evidence to suggest that the Salem Witch trials were brought about following outbreaks of ergotism.Medically useful alkaloids have, however, been isolated, and the most useful of these are the alkaloids ergometrine and it's methylated derivative methyl etgometrine. Both of these compounds stimulate contractionin of uterine smooth muscle and can also be used as vasoconstrictors to control excessive bleeding after childbirth6.4.4 Gibberellins
The gibberellins are a group of diterpenoid compounds containing 19 or 20 carbon atoms and are capable of promoting numerous developmental include the induction of bolting, production of hydrologic enzymes and stimulation of both cell elongation and cell division. These secondary metabolites are biosynthesized form mevelonic acid by Gibberella fujikora, though they have also been isolated from Sphacaloma nonprofits, Neurospora crassa, Rhizobium bordello and Azospirillium lipoferrum. They have numerous agricultural applications, including their use in malting, fruit ripening and improving fruit set and size . On an industrial scale, the most important production organism is G. families, from which mutated strains secrete gibberellins at gram per litre quantities.
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