| crude oil utilization by fungi. | sixty fungal isolates, 34 obtained by a static enrichment technique from soils of northern canadian oil-producing areas and 26 from culture collections, were screened for their ability to grow on n-tetradecane, toluene, naphthalene, and seven crude oils of varying composition. forty cultures, including 28 soil isolates, were capable of growth on one or more crude oils. the genera most frequently isolated from soils were those producing abundant small condida, e.g. penicillium and verticillium sp ... | 1979 | 436012 |
| enhancement of cyclosporin production in a tolypocladium inflatum strain after epichlorohydrin treatment. | following treatment of conidia of the cyclosporin producer fungus, tolypocladium inflatum, with 0.15 m epichlorohydrin, strain m6 was isolated. the new strain exhibited a similar growth rate to the parent organism but more extensive conidiation and several-fold higher overall cyclosporin production. strain m6 reached titres of 318 mg l-1 cyclosporin a in agar cultures, whereas in liquid medium it produced 140 mg l-1 cyclosporin a and 68 mg l-1 cyclosporin c. it also maintained a steady volumetri ... | 1990 | 1366383 |
| pigmented variants of tolypocladium inflatum in relation to cyclosporin a production. | we have isolated four distinct colony types of the fungus tolypocladium inflatum, the producer of the immunosuppressive agent cyclosporin a: morphologically normal white, red, and orange colonies and morphologically diverse tiny brown colonies. in liquid cultures, white normal and brown colonies developed into yellow broths. the broth of the brown colony had a low final ph and low cyclosporin production, whereas orange and red colonies had dark brown and even black broths with higher final ph an ... | 1990 | 1366746 |
| dynamics of l-valine in relation to the production of cyclosporin a by tolypocladium inflatum. | we report the kinetics of endogenous l-valine in the fungus tolypocladium inflatum, in an effort to understand the enhancing effect of externally supplemented l-valine on the production of the immunosuppressant cyclosporin a (cya) in chemically defined medium. in a batch laboratory stirred reactor cultivation, the concentration of intracellular l-valine increased by up to four times between the end of the exponential phase and the beginning of the stationary phase when the medium was supplemente ... | 1991 | 1367231 |
| fk-506 binding protein from tolypocladium inflatum: resistance of fkbp/fk-506 complex against proteolysis. | a 12-kda peptidyl-prolyl-cis/trans-isomerase was purified 225-fold to homogeneity from the cyclosporin producing fungus tolypocladium inflatum. the enzyme is highly sensitive to the immunosuppressant fk-506 but not to cyclosporin and thus belongs to the class of fk-506 binding proteins (fkbp). interestingly the fkbp/fk-506 complex is resistant against proteolytic digestion by the endoproteases gluc and lysc, in contrast to the free fkbp, which is readily cleaved by these proteases. this protecti ... | 1992 | 1371677 |
| ultrastructural changes in culex pipiens larvae treated with tolypin, the insecticidal metabolite of tolypocladium inflatum gams (deuteromycetes). | tolypin, the insecticidal metabolite of the entomopathogenic fungus of the genus tolypocladium, causes knock-down effect followed by high mortality in treated culex pipiens molestus larvae. histopathological changes accompanying the knock-down symptoms were similar in all tissues. mitochondria, the main target in the cells, were destroyed and consecutively changed into vacuoles with the remains of cristae and lysed internal structures. despite destruction of the internal content of individual or ... | 1992 | 1505210 |
| [characteristics of obtaining protoplasts from 2 strains of tolypocladium inflatum subsp. blastosporum]. | the optimal conditions for preparing protoplasts with high yields by using the cells of two (low and high potent) isogenic cyclosporine-producing tolypocladium strains were developed. a specific medium containing 0.5 per cent yeast autolysate (by dry weight) and 3 per cent glucose was used. when grown on this medium the cells of the highly potent strain 847 acquired a yeast-like shape. high yields of protoplasts prepared from the low potent strain 43 mycelium were obtained via prior incubation w ... | 1992 | 1514857 |
| two new cyclophilins from fusarium sambucinum and aspergillus niger: resistance of cyclophilin/cyclosporin a complexes against proteolysis. | two new peptidyl-prolyl-cis/trans-isomerases were purified to homogeneity from fusarium sambucinum and aspergillus niger. they belong to the class of cyclosporin a binding proteins (cyclophilins) and have molecular masses of about 18 kda. as has been shown for other cyclophilins, the isomerase activity of the enzymes is inhibited by cyclosporin a in the nanomolar range. furthermore binding of cyclosporin a prevents proteolytic digestion of the cyclophilin/cyclosporin complexes by the endoproteas ... | 1992 | 1530635 |
| a seventeen kilodaltons peptidyl-prolyl cis-trans isomerase of the cyclosporin-producer tolypocladium inflatum is sensitive to cyclosporin a. | a peptidyl-prolyl cis-trans isomerase (ppiase) was purified to homogeneity about 24-fold from the cyclosporin-producing fungus tolypocladium inflatum. the molecular mass of the enzyme was in the range of 17 kdaltons. remarkably, the enzyme could be inhibited by cyclosporin a in the nanomolar range as has been shown for numerous other cyclophilins from eukaryotic organisms. this indicates, that tolypocladium inflatum must possess a self protection system in order to survive in the presence of cyc ... | 1992 | 1556019 |
| enzymatic biosynthesis of cyclosporin a and analogues. | the final assembly of the undecapeptide chain of cyclosporin a and its cyclization is accomplished in beauveria nivea by cyclosporin synthetase. this multienzyme is the largest integrated enzyme structure so far reported. its size has been estimated at approximately 1,400 kda by two different methods: 1), by 3% sds-page using the related multienzymes acv synthetase and gramicidin s synthetase 2 as references (420 and 556 kda, respectively); and 2), by cscl density gradient centrifugation experim ... | 1992 | 1637876 |
| structure of ergokonin c, a new carboxysterol antifungal antibiotic from a tolypocladium inflatum mutant. | | 1991 | 1798724 |
| cell-free biosynthesis of cyclosporin a and analogues. | the final assembly of the 11-peptide chain of cyclosporins and its cyclization is accomplished in the producer beauveria nivea by cyclosporine synthetase. this multienzyme represents the largest integrated enzyme structure reported so far. its size has been estimated to approximately 1,500 kda by sds-page. some enzyme bound linear peptides could be isolated and identified. all of them represent partial sequences of cyclosporin a starting with d-alanine. these peptides were bound by thioester lin ... | 1991 | 1820050 |
| formation of cyclosporins by tolypocladium inflatum. | submerged cultures of the low-production strain of tolypocladium inflatum dsm 63544 formed a mixture of cyclosporins (cs) consisting of cs-a, cs-b, "cs-3" and "cs-4". glucose, sucrose and maltose were highly favored for biomass production but provided a different physiological state necessary for cs biosynthesis. not only the magnitude of cs production but also the proportion of individual components of the cs mixture were affected by the c source. intensive cs synthesis was in correlation with ... | 1991 | 1841870 |
| selective 13c-labelling of cyclosporin a. | cyclosporin a is biosynthetically labelled with 13c by growing an overproducing strain of tolypocladium inflatum on minimal media containing either [1-13c]-, [2-13c]-, [3-13c]- or [6-13c]glucose as the only carbon source. nmr analysis of the 13c-labelled peptide showed a labelling pattern in which 13c occurs at specific sites. these can be predicted by consideration of the relevant biosynthetic pathways. quantitation of the site-specific enrichments revealed that the 13c-label incorporation is e ... | 1991 | 1868850 |
| isolation of (4r)-4-[(e)-2-butenyl]-4-methyl-l-threonine, the characteristic structural element of cyclosporins, from a blocked mutant of tolypocladium inflatum. | by mutagenic treatment of a strain of tolypocladium inflatum, a cyclosporin non-producing mutant was obtained which accumulated the characteristic building unit of cyclosporins, (4r)-4-[(e)-2-butenyl]-4-methyl-l-threonine (abbreviation bmt; systematic name: (2s,3r,4r,6e)-2-amino-3-hydroxy-4-methyl-6-octenoic acid) in free form. the isolation from a culture filtrate was performed by extraction, chromatographic separation and final crystallization from methanol - water. the structure and stereoche ... | 1990 | 2116402 |
| isolation and partial characterization of cyclosporin synthetase from a cyclosporin non-producing mutant of beauveria nivea. | cyclosporin synthetase was isolated from a cyclosporin non-producing mutant of beauveria nivea, strain yp 582. the enzyme has a molecular mass in the range of active cyclosporin synthetase and also contains 4'-phosphopantetheine as a prosthetic group. it is able to activate all constituent amino acids of cyclosporin a as thioesters and to carry out specific n-methylation reactions. overall synthesis of the undecapeptide cyclosporin a in the presence of all necessary substrates was not observed, ... | 1990 | 2291810 |
| production of cyclosporins by tolypocladium niveum strains. | nine strains of tolypocladium niveum (= inflatum) were compared for their production of cyclosporins. two of the strains, which were originally from the parental nrrl 8044 strain, were among the lower producers, while seventeen tolypocladium strains belonging to seven other species produced no detectable cyclosporins. variable cyclosporin production was observed initially. once extraction and quantitation methods had been established, spore inoculum density and cultural morphology and carbon and ... | 1990 | 2327746 |
| sensitivity to cyclosporin a is mediated by cyclophilin in neurospora crassa and saccharomyces cerevisiae. | cyclosporin a, a cyclic fungal undecapeptide produced by tolypocladium inflatum, is a potent immunosuppressive drug originally isolated as an antifungal antibiotic. cyclosporin a (csa) is widely used in humans to prevent rejection of transplanted organs such as kidney, heart, bone marrow and liver. the biochemical basis of csa action is not known: its primary cellular target has been suggested to be calmodulin, the prolactin receptor or cyclophilin, a csa-binding protein originally isolated from ... | 1989 | 2531848 |
| cyclosporins--new analogues by precursor directed biosynthesis. | cyclosporin a (ciclosporin), a potent and clinically important immunosuppressive drug (sandimmun), represents the main component of a group of over 25 closely related, cyclic undecapeptides produced by the fungus tolypocladium inflatum. by feeding experiments using dl-alpha-allylglycine as precursor, specific incorporation in position 2 was attained leading to [allylgly2]cyclosporin a. exogenously supplied l-beta-cyclohexylalanine results in the almost exclusive production of [mecyclohexylala1]c ... | 1989 | 2722674 |
| cell-free biosynthesis of new cyclosporins. | an enzyme preparation, isolated from extracts of the fungus beauveria nivea (previously designated tolypocladium inflatum), is able to synthesize cyclosporins (cy's) in vitro. at suboptimal temperature it was possible to yield about 50 micrograms of cya per ml. the enzyme also produces several of the naturally occurring congeners of cya, such as the cy's b, c, d, g, m, o, q, u and v and some of the analogues known to be produced by the fungus via precursor directed biosynthesis, like dihydro-cya ... | 1989 | 2759908 |
| the effect of tolypin in tolypocladium niveum crude extract against mosquito and blackfly larvae in the laboratory. | the efficacy of tolypin against mosquito and blackfly larvae was studied under laboratory conditions. it was tested against culex molestus, aedes aegypti, anopheles maculipennis, simulium noelleri and odagmia ornata. a concentration 0.1 mg/ml caused 100% mortality in all species tested and a concentration 0.001 mg/ml caused 100% mortality only in the two species of blackflies used within 24 hours. | 1988 | 2906895 |
| therapeutic strategies in autoimmune disease: cyclosporin a as a model agent. | cyclosporin a is the derivative of the cyclic undecapeptide which is produced by 2 strains of fungi, cylindrocapon lucidum booth and tolypocladium inflatum gams. the drug has achieved widespread use in the treatment of organ transplant recipients as a vanguard against rejection, and currently is being evaluated as an immunosuppressive agent for the therapy of primary autoimmune phenomena as well. its mechanism of action, and application to the treatment of rheumatologic disorders will be discuss ... | 1988 | 2979810 |
| dihydrocyclosporin d in sheep: haemodynamic and renal effects. | 1. this study was designed to test the haemodynamic and renal effects in sheep of dihydrocyclosporin d (dcyd), an immunosuppressant agent derived from the fungus tolypocladium inflatum gams. 2. dcyd was infused for 5 days at 12 mg/kg per day. mean arterial pressure (map) was elevated after 24 h, but thereafter returned to control levels. heart rate was significantly elevated throughout the infusion and was still high 24 h postinfusion. cardiac output rose after 5 days, but total peripheral resis ... | 1988 | 3078280 |
| enzymatic synthesis of cyclosporin a. | an enzyme fraction, isolated from crude extracts of the fungus tolypocladium inflatum, strain 7939/f, is able to synthesize the undecapeptide cyclosporin a. the formation of cyclosporin a was monitored by incorporation of the radiolabeled constituent amino acids of cyclosporin a or by using s-adenosyl-l-[14c-methyl] methionine. the structure of cyclosporin a, synthesized enzymatically in vitro, was confirmed by chromatographic comparison with the authentic compound and by amino acid analyses. re ... | 1987 | 3693349 |
| biosynthesis of cyclosporin a: partial purification and properties of a multifunctional enzyme from tolypocladium inflatum. | an enzyme fraction most probably involved in the biosynthesis of cyclosporin a was purified 540-fold from tolypocladium inflatum. the enzyme was capable of forming covalent enzyme-substrate complexes and catalyzed the atp-pyrophosphate exchange reactions dependent on the unmethylated constituent amino acids of cyclosporin a. evidence was obtained that covalent binding of substrate amino acids occurred via thioester linkage. furthermore, the n-methylation of thio-esterified valine, leucine, and g ... | 1986 | 3955013 |
| cloning and sequencing of a cyclophilin gene from the cyclosporin producer tolypocladium niveum. | the gene of a 19 kda cyclophilin of tolypocladium niveum was isolated and sequenced. the open reading frame of 956 bp is interrupted by four introns of 76, 221, 58, and 61 bp size. 101 nucleotides upstream of the start codon atg we found a putative promoter region containing a tata and a caat box. the predicted amino acid sequence shows high identity to other cyclophilins, especially to the cyclophilin a family members of eucaryotic and procaryotic origin. similar to the case of n. crassa we fou ... | 1995 | 7663412 |
| mathematical modeling of the production of cyclosporin a by tolypocladium inflatum: effect of l-valine. | a mathematical model was developed to describe the kinetics of submerged fungal growth, consumption of nutrients, and production of the immunosuppressant drug, cyclosporin a (cya). special emphasis was placed on the experimentally observed stimulatory effect of l-valine on cya production. the proposed model was based on kinetic information and emerging mechanistic data on cya biosynthesis. it was assumed that l-valine acts as both precursor and inducer of the cya-synthesizing multienzyme (cya sy ... | 1993 | 7763411 |
| dynamic response of immobilized cells to pulse addition of l-valine in cyclosporin a biosynthesis. | a feeding strategy for l-valine was tested in the production of cyclosporin a (cy a), a powerful immunosuppressive secondary metabolite, in celite-immobilized cells of the fungus tolypocladium inflatum. this system has been previously shown to have promise over conventional submerged systems. significant increase in cy a biosynthesis was manifested in the immobilized cells when l-valine was added at 108 h (system c) and at 156 h (system d) during the exponential growth phase. however, no clearly ... | 1993 | 7763467 |
| disruption of the cyclosporin synthetase gene of tolypocladium niveum. | cyclosporin a is a potent and clinically-important immunosuppressive drug (sandimmunr). it is produced by the fungus tolypocladium niveum. a transformation system for t. niveum atcc34921 based on hygromycin selection was established. in order to obtain a t. niveum promoter, the cyclophilin gene was isolated using the neurospora crassa gene as probe. a plasmid vector was constructed in which the promoter region of the t. niveum cyclophilin gene was fused to a bacterial hygromycin phosphotransfera ... | 1994 | 7874740 |
| the peptide synthetase catalyzing cyclosporine production in tolypocladium niveum is encoded by a giant 45.8-kilobase open reading frame. | cyclosporin a, a potent and clinically-important immunosuppressive drug (sandimmunr), is synthesized from its precursor amino acids by cyclosporin synthetase, a single multi-functional enzyme. in this study we report the cloning of the corresponding coding region of this synthetase. it contains an open reading frame of 45.8 kb which encodes a peptide with a calculated m(r) of 1,689,243. the predicted gene product contains 11 amino-acid-activating domains that are very similar to one another and ... | 1994 | 8001164 |
| purification and characterization of eucaryotic alanine racemase acting as key enzyme in cyclosporin biosynthesis. | a specific alanine racemase, which is a key enzyme in the biosynthesis of the undecapeptide cyclosporin a, was purified to electrophoretic homogeneity from the fungus tolypocladium niveum. this is the first enzyme of this kind isolated from a eucaryotic organism. the enzyme catalyzes the reversible racemization of alanine and requires pyridoxal phosphate as the exclusive cofactor. km values for l- and d-alanine were found to be 38 and 2 mm, respectively. maximal reaction velocity was observed at ... | 1994 | 8175682 |
| biosynthesis of the unusual amino acid (4r)-4-[(e)-2-butenyl]-4-methyl-l-threonine of cyclosporin a. identification of 3(r)-hydroxy-4(r)-methyl-6(e)-octenoic acid as a key intermediate by enzymatic in vitro synthesis and by in vivo labeling techniques. | the biosynthesis of (4r)-4-[(e)-2-butenyl]-4-methyl-l-threonine (abbreviation: bmt, systematic name: 2(s)-amino-3(r)-hydroxy-4(r)-methyl-6(e)-octenoic acid) is proposed to involve two principal phases: the formation of a polyketide backbone and a subsequent transformation process to the final product. here we report on the identification of 3(r)-hydroxy-4(r)-methyl-6(e)-octenoic acid as the end product of the first phase. the primary indication of 3(r)-hydroxy-4(r)-methyl-6(e)-octenoic acid as t ... | 1993 | 8253730 |
| a unique repeated dna sequence in the cyclosporin-producing strain of tolypocladium inflatum (atcc 34921). | recombinant lambda clones containing repeated dna sequences were isolated from the cyclosporin a-producing fungus tolypocladium inflatum (atcc 34921) by differential hybridization with total fungal dna and rdna probes. from this survey 1% of the lambda clones appeared to contain repeated sequences. subsequent analysis led to the identification of a dispersed repetitive dna element. it was named cpa element (cyclosporin production associated) and appears to be strain specific, since it is absent ... | 1995 | 8574905 |
| restless, an active ac-like transposon from the fungus tolypocladium inflatum: structure, expression, and alternative rna splicing. | elements of the hat transposon family, such as the maize activator (ac), have been discovered in a large number of eukaryotic species. this type of class ii transposon, present in both plants and animals, has not been previously detected in any fungal organism. however, using a differential screening method to detect repetitive dna, we have identified a hat transposon in the hyphomycete tolypocladium inflatum. the transposon, which we named restless, is 4,097 bp long, carries 20-bp inverted repe ... | 1996 | 8887685 |
| growth and cyclosporin a production by an indigenously isolated strain of tolypocladium inflatum. | a fungal culture isolated from a local soil sample which showed antifungal activity and produced cyclosporin a, was identified as tolypocladium inflatum. the culture grew best in a medium containing 1% maltose (ph 5-6) when inoculated with a one-day-old inoculum at 2% (v/v) concentration. under batch fermentation conditions, growth and cyclosporin a production were better in complex media (24.6 g biomass and 205 mg cyclosporin a per liter) in comparison with synthetic media (6.84 g biomass and 3 ... | 1996 | 9131797 |
| cyclosporin c is the main antifungal compound produced by acremonium luzulae. | a strain of acremonium luzulae (fuckel) w. gams was selected in screening new microorganisms for biological control of fruit postharvest diseases, especially gray and blue mold diseases on apples and strawberries. this strain manifests a very strong activity against a large number of phytopathogenic fungi. in this work, the product responsible for this antifungal activity was isolated from modified sabouraud dextrose broth cultures of a. luzulae. it was purified to homogeneity by reverse-phase c ... | 1997 | 9143111 |
| [effect of cyclosporin a and amphotericin b on protoplasts of tolypocladium inflatum]. | when added to the suspension of washed cells of tolypocladium inflatum (cyclosporine-producing organism) in a concentration up to 100 micrograms/ml, cyclosporine a had no effect on permeability of the cell covers as judged by the quantity of the metabolites with the absorption maxima at 260 nm that leaked to the medium. when cyclosporine was added to the suspension of the t-inflatum cell protoplasts there was a significant increase in the metabolites leaking. impairment of the permeability of th ... | 1997 | 9265464 |
| development of sporulation/immobilization method and its application for the continuous production of cyclosporin a by tolypocladium inflatum. | an efficient sporulation/immobilization procedure for immobilized fungal cell culture was developed by modifying an existing immobilized technique to shorten the time and number of steps for sporulation. this method was applied to an immobilized-cell perfusion bioprocess (ipb) for continuous production of cya, an intracellular secondary metabolite produced by a filamentous fungus, tolypocladium inflatum. in the ipb, the fungal cells were immobilized in the pores of celite beads (100-500 microm) ... | 1997 | 9376111 |
| cyclosporins: immunosuppressive drugs with anti-hiv-1 activity. | cyclosporin a was introduced into clinical use in the late 1970s to reduce graft rejection after organ transplantation. this drug, a cyclic undecapeptide metabolite of the fungus tolypocladium inflatum, interferes with lymphokine biosynthesis, hence its immunosuppressive activity. recently, it has become clear that cyclosporins are also inhibitors of hiv-1 replication. immunosuppressive and antiviral activities are distinct functions of the cyclosporins, but both functions require an interaction ... | 1995 | 9415163 |
| effects of the immunosuppressive drugs csa and fk506 on intracellular signalling and gene regulation. | the isolation of cyclosporin a (csa) from cultures of the fungus tolypocladium inflatum and its subsequent elucidation of immunosuppressive properties by borel et al. (1) was of great clinical consequence. in the early 80s csa was introduced in the field of organ transplantation resulting in extraordinary improvements of graft survival. csa has become a first choice drug for patients with allograft organs. the discovery of fk506 by kino et al. (2) as a novel immuno-suppressant and its introducti ... | 1997 | 9442391 |
| evidence for circular transposition derivatives from the fungal hat-transposon restless. | the structure and function of eukaryotic hat-transposons has already been elucidated; however, their transposition mechanism is barely understood. we recently have discovered restless, a fungal member of the hat-transposon family, which shows transposition in its host tolypocladium inflatum. investigations of two strains from t. inflatum, carrying either about 15 copies or only a single copy of the restless element, indicate the presence of circular transposition intermediates. using pcr technol ... | 1998 | 9745022 |
| distribution of the fungal transposon restless: full-length and truncated copies in closely related strains. | the fungal transposon restless of tolypocladium inflatum atcc 34921 is a member of the hat family of mobile dna elements. in order to study the distribution of this transposon we have looked at 13 fungal strains, most of which are taxonomically related to strain atcc 34921. three strains, which show identical banding patterns in a comparative rapd analysis with strain atcc 34921, similarly carry multiple copies of restless. in addition, 1 t. inflatum strain and 2 beauveria nivea strains contain ... | 1998 | 9974222 |
| tagging of a nitrogen pathway-specific regulator gene in tolypocladium inflatum by the transposon restless. | restless is an endogenous hat transposon found in the cyclosporin-producing fungus tolypocladium inflatum. this element is present in about 15 copies in a particular strain (atcc34921) which was used for successful gene tagging. we have isolated a t. inflatum mutant with a defect in nitrogen metabolism. this mutant carries a copy of the restless element in a gene encoding a c6 zinc-finger protein. the deduced amino acid sequence of the gene product shows a significant similarity to the nit4 prot ... | 2000 | 10778749 |
| methylation of the foreign transposon restless in vegetative mycelia of neurospora crassa. | methylation of foreign and/or repeated sequences in the filamentous fungus neurospora crassa is believed to be directed against invading transposable elements. to test this hypothesis, the fate of a transposon in n. crassa was investigated. vectors were constructed which carried the transposon restless, an active class-ii element isolated from the fungus tolypocladium inflatum. these vectors were introduced into n. crassa strains by protoplast transformation. two strategies were employed: (1) ec ... | 2000 | 10794177 |
| total synthesis of cyclosporin o both in solution and in the solid phase using novel thiazolium-, immonium-, and pyridinium-type coupling reagents: bemt, bdmp, and bep. | cyclosporin o (1), an extensively n-methylated immunosuppressive cyclic undecapeptide isolated from tolypocladium inflatum gams, was synthesized in 20-23% overall yield via 4 + 7 segment condensation and cyclization by the combined utilization of novel thiazolium- and immonium-type peptide coupling reagents 2-bromo-3-ethyl-4-methyl thiazolium tetrafluoroborate (bemt) and 5-(1h-benzotriazol-1-yloxy)-3,4-dihydro-1-methyl 2h-pyrrolium hexachloroantimonate (bdmp) as well as compound 2-bromo-1-ethyl ... | 2000 | 10814183 |
| structure and localization of cyclosporin synthetase, the key enzyme of cyclosporin biosynthesis in tolypocladium inflatum. | the electron microscopic image of native cyclosporin synthetase molecules showed large globular complexes of 25 nm in diameter, built up by smaller interconnected units. compartmentation of cyclosporin synthetase and the functionally interconnected d-alanine racemase was revealed after sucrose density gradient centrifugation of subcellular fractions and immunoelectron microscopy. a considerable proportion of cyclosporin synthetase and d-alanine racemase was detected at the vacuolar membrane. the ... | 2001 | 11685373 |
| ds-like restless deletion derivatives occur in tolypocladium inflatum and two foreign hosts, neurospora crassa and penicillium chrysogenum. | single copies of the transposon restless from tolypocladium inflatum were introduced into neurospora crassa and penicillium chrysogenum. excision of restless from its donor site was investigated in n. crassa and in p. chrysogenum using direct selective conditions. in n. crassa, forward selection was also analyzed. deleted restless elements were frequently obtained in addition to the expected complete removal of restless from its donor site. similar deleted elements were also identified in t. inf ... | 2002 | 11848679 |
| spermidine as a potential biosynthetic precursor to the 1,5-diazabicyclo[4:3:o]nonene residue in the efrapeptins. | efrapeptins are a group of microheterogeneous polypeptide antibiotics produced by the fungus tolypocladium niveum, which are potent inhibitors of mitochondrial f1-atpase. efrapeptins contain an unusual 1,5-diazabicyclo[4:3:0]nonene (dbn) residue at the c-terminus. this study is driven by the hypothesis that the dbn residue could, in principle, arise by oxidative cyclization of a spermidine moiety. electrospray ionization mass spectrometry of the peptide antibiotics 'elvapeptins' from t niveum es ... | 2001 | 11892846 |
| [ciclosporin]. | ciclosporin, produced by the fungus tolypocladium inflatum gams is endowed with potent immunosuppressive properties. ciclosporin interferes with nuclear factors of activated t-cells, specifically by preventing cytokine gene transcription, particularly interleukin-2, which induces maturation and proliferation of helper t-cells. initially, a traditional formulation of sandimmun(r) was used, but its oral bioavailability varies. absorption of a new formulation, neoral(r), is significantly better and ... | 2002 | 12055538 |
| [streptomyces griseolus # 182--a novel organism producing oligomycin antibiotics. taxonomy, fermentation, and isolation]. | target screening of natural immunosuppressors resulted in isolation of a strain of streptomyces griseolus (no. 182) producing a complex of antifungal antibiotics. the strain proved to be an aerobe with the growth temperature of 26 to 28 degrees c. morphological features and physiological properties of the strain were studied. scanning electron microscopy revealed smooth, oval spores 1.10-1.25 mu in size. the findings showed that the strain belonged to streptomyces griseolus. unlike the previousl ... | 2003 | 14558413 |
| alternative splicing of transcripts of the transposon restless is maintained in the foreign host neurospora crassa and can be modified by introducing mutations at the 5' and 3' splice sites. | the primary transcript of the transposon restless from tolypocladium inflatum undergoes an unusual mechanism of alternative splicing by employing either of two 3' "cag" splice sites. these are separated by only four nucleotides, thus generating two different splice products, which differ in their coding capacity. to analyse whether this alternative splicing occurs in its natural host exclusively, we introduced the transposon into the heterologous host neurospora crassa. in addition to the wild - ... | 2004 | 15148624 |
| [lovastatin effect on ergosterol production and growth of tolypocladium inflatum 106]. | the effect of lovastatin on tolypocladium inflatum 106 was studied. the strain was shown to be highly sensitive to lovastatin when its mic was determined by the agar diffusion method and under submerged conditions that was considered possible to use the strain as a test culture in screening of new natural compounds with hypolipidemic action and to study its specificity. it was demonstrated that the effect of lovastatin on ergosterol synthesis in t. inflatum 106 was of specific dose-dependent pol ... | 2004 | 15460015 |
| [screening of natural compounds with hypolipidemic activity]. | in the screening programme for natural hypolipidemic compounds 702 strains of soil microorganisms were tested and 25 of them were selected because of their ability to produce compounds inhibiting sterol synthesis in hep g2 hepatoma cells. the compounds were estimated in the microbiological model with tolypocladium inflatum 106 as the test microbe. the 2nd stage of the screening resulted in isolation of 13 strains producing compounds with high hypolipidemic activity, analogous to or higher than t ... | 2004 | 15727139 |
| rheology and hydrodynamic properties of tolypocladium inflatum fermentation broth and its simulation. | a physico-chemical, two phase simulated pseudoplastic fermentation (spf) broth was investigated in which solka floc cellulose fibre was used to simulate the filamentous biomass, and a mixture of 0.1% (w/v) carboxymethyl cellulose (cmc) and 0.15 m aqueous sodium chloride was used to simulate the liquid fraction of the fermentation broth. an investigation of the rheological behaviour and hydrodynamic properties of the spf broth was carried out, and compared to both a fungal tolypocladium inflatum ... | 2005 | 15744504 |
| identification, cloning and expression of pseudomonas aeruginosa ps-x putative urate oxidase gene in escherichia coli. | in a previous study we reported for the first time the isolation and characterization ofurate oxidase enzyme from pseudomonas aeruginosa. in this work we isolated and cloned a 1.350 kilobase dna fragment that encode a putative urate oxidase gene from the genomic library of p. aeruginosa ps-x. the nucleotide sequence of the cloned dna insert revealed an open reading frame that encodes a protein of a molecular weight of 54.0 kda. the cloned dna fragment showed an uricolytic activity when expressed ... | 2004 | 15790071 |
| microbial biomass, community structure and metal tolerance of a naturally pb-enriched forest soil. | the effect of long-term elevated soil pb levels on soil microbiota was studied at a forest site in norway, where the soil has been severely contaminated with pb since the last period of glaciation (several thousand years). up to 10% pb (total amount, w/w) has been found in the top layer. the microbial community was drastically affected, as judged from changes in the phospholipid fatty acid (plfa) pattern. specific plfas that were high in pb-enriched soil were branched (especially br17:0 and br18 ... | 2005 | 16328661 |
| morphological and genetic characterization of a cultivated cordyceps sinensis fungus and its polysaccharide component possessing antioxidant property in h22 tumor-bearing mice. | cordyceps sinensis, one of the most precious traditional chinese medicines, possesses the antitumor activity, antioxidant activity and the capability of modulating the immune system. in the present study, a fungus strain g1 isolated from wild c. sinensis was identified and initially characterized. a phylogenetic tree was generated based on the sequences of the internal transcribed spacer (its) region of related fungi. the analysis of its sequence showed that fungus g1 was clustered together with ... | 2006 | 16492382 |
| nucleotide excision repair and photoreactivation in the entomopathogenic fungi beauveria bassiana, beauveria brongniartii, beauveria nivea, metarhizium anisopliae, paecilomyces farinosus and verticillium lecanii. | to compare the dna repair capabilities of the entomopathogenic fungus (epf) bassiana to the epf beauveria brongniartii, beauveria nivea, metarhizium anisopliae, paecilomyces farinosus, verticillium lecanii, and the fungi aspergillus niger and neurospora crassa. | 2006 | 16629997 |
| pathophysiological response of rhesus monkey kidney epithelial cells exposed to cyclosporine a. | cyclosporine a (csa) is extracted from tolypocladium inflatum gams, which is metabolized through the superfamily of hepatic isoenzymes p-450. csa has a mean life of 6.4-8.7 h, although this varies among different individuals. ninety percent of the drug is excreted through biliary excretion and only 6% appears unchanged in the urine. the exact mechanism of action of csa is unknown; however, csa has the ability to act on the immune system by blocking the biosynthesis of some lymphokines produced b ... | 2006 | 16817590 |
| effect of solvent concentration on the extraction kinetics and diffusivity of cyclosporin a in the fungus tolypocladium inflatum. | the kinetics of solid-liquid extraction and extraction yields of the immunosuppressant drug cyclosporin a (cya) from the mycelia of tolypocladium inflatum were examined in this study. a 2 l stirred, baffled vessel was used to extract cya from wet mycelia mass. three different organic solvents were used, namely, methanol, acetone, and isopropanol at different concentrations in aqueous mixtures at room temperature. it was found that the best solvent was acetone at 50% v/v concentration achieving 1 ... | 2007 | 16948167 |
| effect of temperature on the extraction kinetics and diffusivity of cyclosporin a in the fungus tolypocladium inflatum. | the influence of temperature on the extraction kinetics of cyclosporin a (cya) from the mycelia of tolypocladium inflatum was examined in this study. the extraction of cya from mycelia was performed in a 2-l stirred, baffled vessel using 30% v/v aqueous methanol. the temperature range used was from 5 to 45 degrees c. a linear relationship was found between the extraction yield of cya and temperature. as the temperature increased, the yield of cya increased with a maximum cya yield of 18.3% obtai ... | 2007 | 17009335 |
| cyclosporine a: a review of current oral and intravenous delivery systems. | as early as 1978, the immunosuppressive effect of cyclosporine a (csa), a metabolite of the fungus tolypocladium inflatum (borel, 1989), was reported to be effective in inhibiting organ rejection in patients receiving kidney transplants from mismatched cadaver donors (calne et al., 1978) and in the treatment of graft-versus-host disease in patients with acute leukemia following bone marrow transplants (powles et al., 1978). today, csa is still indicated to prevent rejection following solid organ ... | 2007 | 17454054 |
| application of factorial experimental designs for optimization of cyclosporin. a production by tolypocladium inflatum in submerged culture. | a sequential optimization strategy based on statistical experimental designs was employed to enhance the production of cyclosporin a (cya) by tolypocladium inflatum dsmz 915 in a submerged culture. a 2-level plackett-burman design was used to screen the bioprocess parameters significantly influencing cya production. among the 11 variables tested, sucrose, ammonium sulfate, and soluble starch were selected, owing to their significant positive effect on cya production. a response surface methodolo ... | 2007 | 18167438 |
| kinetics of cell growth and cyclosporin a production by tolypocladium inflatum when scaling up from shake flask to bioreactor. | the kinetics of cell growth and cyclosporin a (cyc a) production by tolypocladium inflatum were studied in shake flasks and bioreactors under controlled and uncontrolled ph conditions. in the case of the shake flask, the production time was extended to 226 h and the maximal antibiotic concentration was 76 mg/l. when scaling up the cultivation process to a bioreactor level, the production time was reduced to only 70 h with a significant increase in both the cell growth and the antibiotic producti ... | 2008 | 18239429 |
| [diversity of facultatively anaerobic microscopic mycelial fungi in soils]. | the numbers of microscopic fungi isolated from soil samples after anaerobic incubation varied from tens to several hundreds of cfu per one gram of soil; a total of 30 species was found. this group is composed primarily of mitotic fungi of the ascomycete affinity belonging to the orders hypocreales (fusarium solani, f. oxysporum, fusarium sp., clonostachys grammicospora, c. rosea. acremonium sp., gliocladium penicilloides, trichoderma aureoviride, t. harzianum, t. polysporum, t. viride. t. koning ... | 2008 | 18365728 |
| comparative studies of physiological and environmental effects on the production of cyclosporin a in suspended and immobilized cells of tolypocladium inflatum. | process improvement of the production of cyclosporin a (cy a), a powerful immunosuppressive fungal metabolite, has been undertaken by analyzing suspended and immobilized cell cultures in parallel. conidiospores of the producer microorganism, tolypocladium inflatum, were entrapped into porous celite particles. easier germination of the entrapped spores and more active growth of the immobilized cells were manifested when compared with free cell cultures initiated with spores or with mycelial inocu ... | 1991 | 18597363 |
| spore inoculum optimization to maximize cyclosporin a production in tolypocladium niveum. | the cyclic undecapeptide, cyclosporin a (cya), is one of the most commonly prescribed immunosuppressive drugs. it is generated nonribosomally from a multifunctional cyclosporin synthetase enzyme complex by the filamentous fungus tolypocladium niveum. in order to maximize the production of cya by wild-type t. niveum (atcc 34921), each of three culture stages (sporulation culture, growth culture, and production culture) were sequentially optimized. among the three potential sporulation media, the ... | 2008 | 18633291 |
| the tolypocladium inflatum cpa element encodes a recq helicase-like gene. | previously, a repetitive cpa element was discovered in the genome of the filamentous fungus tolypocladium inflatum; however, no further characterization was technically possible at that time. in this study, pcr amplification was used to detect a 4 kb conserved portion of the cpa element that appeared to be present in most, if not all, genomic cpa elements. the amplicons included a large open reading frame that was most similar to a recq helicase-like gene from metarhizium anisopliae. the repetit ... | 2008 | 18792048 |
| a novel medium for the enhanced production of cyclosporin a by tolypocladium inflatum mtcc 557 using solid state fermentation. | cyclosporin a (cya) produced by tolypocladium inflatum is a promising drug owing to its immunosuppressive and antifungal activities. from an industrial point of view, the necessity to obtain a suitable and economic medium for higher production of cya was the aim of this work. the present study evaluated the effect of different fermentation parameters in solid state fermentation, such as selection of solid substrate, hydrolysis of substrates, initial moisture content, supplementation of salts, ad ... | 2009 | 19494693 |
| combination strategy to increase cyclosporin a productivity by tolypocladium niveum using random mutagenesis and protoplast transformation. | the cyclic undecapeptide cyclosporin a (cya), one of the most valuable immunosuppressive drugs, is produced nonribosomally by a multifunctional cyclosporin synthetase enzyme complex by the filamentous fungus tolypocladium niveum. to increase cya productivity by wild-type t. niveum (atcc 34921), random mutagenesis was first performed using an antifungal agar-plug colony assay (apca) selection approach. this generated a mutant strain producing more than 9-fold greater cya than the wild-type strain ... | 2009 | 19809241 |
| statistical optimization for improved production of cyclosporin a in solid-state fermentation. | this work evaluates the effect of different amino acids on production of cya production in solid-state fermentation that was previously optimized for different fermentation parameters by one-factor-at-a-time for the maximum production of cya by tolypocladium inflatum mtcc 557. based on the plackett-burman design, glycerol, ammonium sulfate, fecl3, and inoculum size were selected for further optimization by response surface methodology (rsm). after identifying effective nutrients, rsm was used to ... | 2009 | 19996692 |
| [complex of cyclosporins produced by tolypocladium inflatum isolated from soil sample from buriatiia]. | a micromycete culture was isolated from a soil sample of buryatiya and identified as tolypocladium inflatum no. 2. the culture was shown to produce a complex of cyclosporins of unusual component structure: the content of cyclosporin a (55-60%) was the same as that in the substances produced by the majority of the described cultures, the content of cyclosporin b was much higher (about 40%) and the content of cyclosporin c was relatively low (about 3%). an appreciable content of cyclosporin (leu4) ... | 2009 | 20415255 |
| gellan gum as an immobilization matrix for the production of cyclosporin a. | this study explored the use of gellan gum as an immobilization matrix for production of cyclosporin a (cya) by immobilized spores and mycelia of tolypocladium inflatum mtcc 557. different carriers, such as gellan gum, sodium alginate, celite beads and silica, were tested as immobilization carriers, along with the role of the carrier concentration, biomass weight, number of spore-inoculated beads, and repeated utilization of the immobilized fungus. the maximum cya production was 274 mg/l when usi ... | 2010 | 20668401 |
| production of fumonisins b(2) and b (4) in tolypocladium species. | tolypocladium inflatum is known primarily for its production of the cyclosporines that are used as an immunosuppressive drug. however, we report here the production of the carcinogenic fumonisins b(2) and b(4) by this biotechnologically relevant fungal genus. these mycotoxins were detected in 11 strains tested from three species: tolypocladium inflatum, t. cylindrosporum, and t. geodes. production of fumonisins by fusarium spp. and aspergillus niger is highly medium- and temperature-dependent, s ... | 2010 | 21132348 |
| targeted gene disruption and functional complementation of cytochrome p450 hydroyxlase involved in cyclosporin a hydroxylation in sebekia benihana. | a cyclic undecapeptide-family natural product, cyclosporin a (cya), which is one of the most valuable immunosuppressive drugs, is produced nonribosomally by a multifunctional cyclosporin synthetase enzyme complex in a filamentous fungal strain named tolypocladium niveum. previously, structural modifications of cyclosporins such as a regionspecific hydroxylation at the 4th n-methyl leucine in a rare actinomycetes called sebekia benihana were reported to lead to dramatic changes in their bioactive ... | 2011 | 21301187 |
| cyclosporin a--a review on fermentative production, downstream processing and pharmacological applications. | in present times, the immunosuppressants have gained considerable importance in the world market. cyclosporin a (cya) is a cyclic undecapeptide with a variety of biological activities including immunosuppressive, anti-inflammatory, antifungal and antiparasitic properties. cya is produced by various types of fermentation techniques using tolypocladium inflatum. in the present review, we discuss the biosynthetic pathway, fermentative production, downstream processing and pharmacological activities ... | 2011 | 21447377 |
| isolation and characterization of aphidicolin and chlamydosporol derivatives from tolypocladium inflatum. | six new secondary metabolites including two aphidicolin analogues, inflatins a (1) and b (2), and four chlamydosporol derivatives, inflatins c-f (3-6), have been isolated from the crude extract of tolypocladium inflatum. the structures of 1-6 were determined mainly by nmr experiments, and 4 and 5 were further confirmed by x-ray crystallography. the absolute configurations of c-16 in 1 and c-5 in 3 were deduced via the circular dichroism data of the in situ formed [rh(2)(ococf(3))(4)] complexes, ... | 2011 | 21812410 |
| the potent antimalarial peptide cyclosporin a induces the aggregation and permeabilization of sphingomyelin-rich membranes. | cyclosporin a (csa) is a hydrophobic peptide drug produced by the fungus tolypocladium inflatum. csa is commonly used as an immunosuppressive drug, but it also has antimalarial activity. the immunosuppressive activity of csa is clearly due to its association with specific proteins of immune cells such as cyclophilins. by contrast, the antimalarial properties of this peptide are completely independent of the association with a parasite's cyclophilins. because of its hydrophobicity, csa may intera ... | 2011 | 21692492 |
| synthesis and conformational analysis of efrapeptins. | the efrapeptin family of peptide antibiotics produced by the fungus tolypocladium niveum, and the neo-efrapeptins from the fungus geotrichum candidumare inhibitors of f(1) -atpase with promising antitumor, antimalaria, and insecticidal activity. they are rich in c(α) -dialkyl amino acids (aib, iva, acc) and contain one β-alanine and several pipecolic acid residues. the c-terminus bears an unusual heterocyclic cationic cap. the efrapeptins c-g and three analogues of efrapeptin c were synthesized ... | 2011 | 22147615 |
| Cold activity and tolerance of the entomopathogenic fungus Tolypocladium spp. to UV-B irradiation and heat. | Studies on the stress resistance of insect-pathogenic fungi are very important to better understand the survival of these organisms in the environment. In this study, we examined the cold activity (8 ± 1°C for 7 days), UV-B tolerance (Quaite-weighted UV-B irradiance at 847.90 mW m(-2) for 1, 2, 3, and 4 h), and wet-heat tolerance (45°C for 1, 2, 3, and 4 h) of two isolates of Tolypocladiumcylindrosporum (ARSEF 3392 and 5558), one isolate of Tolypocladium geodes (ARSEF 3275), and two isolates of ... | 2011 | 21925183 |