Penicillium mycotoxins from

Neoxaline, C23H25N5O4, a new metabolite of Aspergillus japonicus, exhibits similarities to oxaline in its i.r. and n.m.r. spectra, and may be an indole derivative, but nothing further is known of its constitution as yet.38a Similarly, three new tremorgenic mycotoxins from Penicillium janthinellum, janthitrems A, B, and C, may also be indole derivatives.386... 

Compounds 8-11 belonged to the bisabolane family of sesquiterpenes. Bisabolane sesquiterpenes are not typical microbial metabolites. Most compounds of this skeletal class have been isolated from numerous terrestrial plants, a basidiomycete [101], sponges [102-103], octocoral [104, 105], and red algae [106], To our knowledge there have been two reports of bisabolanes from fungi. The first report in 1989 was of a mycotoxin from Fusarium sambucinum [107], More recently, mass spectral analysis of the volatile constituents of toxigenic Penicillium roqueforti strains yielded P-bisabolene [108]. 

C30H22O12, Mr 574.50, mp. 278 °C, [a]u -830° yellow, hepatotoxic mycotoxin from Penicillium islan-dicum. L. belongs to the bianthraquinones such as, e. g., rugulosin and skyrin. The biosynthesis proceeds on the polyketide pathway. On being fed daily with I mg toxin per 20 g animal, mice develop liver tumors within 6 months. The toxin accumulates in hepatic mitochondria. In the presence of Mg ions L. binds to double- and single-stranded DNA and inhibits the DNA-de-pendent RNA polymerases. L. has antimicrobial and cytotoxic properties and is active against protozoa. Chromosome breaks are induced in cell cultures. 

C30H31 NO,o, Mr565.58, light yellow cryst., mp. 235 °C (decomp.), [a] -12° (C2H5OH). Mycotoxin from Penicillium viridicatum. Biosynthetically, it is a nona-ketide with a monoterpene unit at C-6. V. is toxic (LD50 rat p.o. 122 mg/kg) and can be ingested with moldy food. 

Ueno Y, Sato N, Ito T, Ueno I, Enomoto M, Tsunoda H (1980) Chronic Toxicity and Hepatocaicinogenicity of (+)-Rugulosin, an Anthaquinoid Mycotoxin from Penicillium Species Preliminary Sinveys in Mice. J Toxicol Sci 5 295... 

Sanakawa, U., The biosynthesis of anthraquinonoid mycotoxins from Penicillium isandicum Sopp and related fungi, in The Biosynthesis of Mycotoxins (P. Steyn, ed.), 357-394, Academic Press, New York, 1980. 

Franck, B. The biosynthesis of ergochromes. In The Biosynthesis of Mycotoxins (P. S. Steyn ed.), pp. 157-191. Academic Press, New York 1980 Leistner, E. Biosynthesis of plant quinones. In The Biochemistry of Plants, Vol. 7, Secondary Plant Products (E. E. Conn, ed.), pp. 403-423. Academic Press, New York 1981 Sankawa, U. The biosynthesis of anthraquinoid mycotoxins from Penicillium islandicum Sopp and related fungi. In The Biosynthesis of Mycotoxins (P. S. Steyn, ed.),pp. 357-394. Academic Press, New York 1980... 

Kozlovsky, A.G., Marfenina, O.E., Vinokurova, N.G., Zhelifonova, V.P. and Adanin, V.M. (1997) Mycotoxins of filamentous fungi of the genus Penicillium, isolated from the soils of the natural and antropogenic breached ecosystems. Microbiologiya (in Russian), 66,112-116. 

The Biosynthesis of Anthraquinonoid Mycotoxins from Penicillium islandicum Sopp and Related Fungi... 

Penicillium expansum is the major producer of the mycotoxins patulin and citrinin. Patulin is a mycotoxin mainly found in apple and apple products. P. expansum grows from 3 to 35°C, with an optimum of 25°C. Patulin is synthesized from 0 to 25°C with its optimum at 25°C. Citrinin is also produced along with patulin by P. expansum. 

Streptoverticillium album K-25l/ the antitumoral bis-indole alkaloids vinblastine and vincristine/ verruculogen, a very potent mycotoxin produced by several Penicillium species and melatonin, a hormone found in all living creatures from algae to humans, just to mention the most important ones. 

Botrytized wines, being produced from mold-affected grapes, might be expected to be contaminated with OTA. Although Botrytis itself has never been reported to produce mycotoxins, associated Penicillium and Aspergillus species might be involved in toxin production. To date, studies on botrytized wine have either not detected or found low OTA levels. 

Six mycotoxins, penitrems A—F [(16a)—(16f)], derived from tryptophan (with loss of the side-chain) and a diterpene unit (with loss of a carbon atom), have been isolated from Penicillium crustosum iSe of these, penitrem A was first isolated15/in 1968 from P. cyclopium, and penitrems B and C in 197l15 from a micro-organism originally presumed to be P. palitans, but now classified as P. crustosum. The occurrence of penitrem A in P. cyclopium has recently been confirmed, and the presence of penitrem B was also demonstrated.156... 

Citreoviridin (79), luteoskyrin (80), and cyclochlorotine (81) are historical mycotoxins studied in Japan. Citreoviridin was isolated as a toxin from Penicillium citreoviride associated with a disease called cardiac beriberi or shoshin kakke .164 Luteoskyrin and cyclochlorotine were isolated from Penicillium islandicum, which was infected into toxic yellowed rice.165 Genes responsible for biosynthesis of these compounds are not obtained. 

Phomopsin A (83 in Figure 18) was isolated from Phomopsis leptostromiformis as the hepatotoxic metabolite responsible for lupinosis, which is a disease in animals caused by ingestion of Lupinus species infected with the fungus.169 Penicillium species produce other significant mycotoxins such as penitrem A (84), PR toxin (85), and rubratoxin B (86).170 Fusarin C (87) and fusaproliferin (88) are known as mycotoxins produced by Fusarium... 

A second stereoselective total synthesis of ( )-eremophilone (243) has been accomplished using 7-epinootkatone (242) as intermediate.109 The latter compound was synthesized from (—)-/3-pinene (241) by modification of the published procedure"0 and subsequently converted into eremophilone (243) by the series of functional-group transformations shown in Scheme 30. A mycotoxin isolated from Penicillium roqueforti has been assigned the highly oxygenated eremophilane structure (244) on the basis of chemical and spectroscopic evidence."1 The structure and... 

Steyn PS Mycotoxins, general view, chemistry and structure. Toxicol Lett 1995 82 843-851. Yamaguchi T, Nozawa K, Hosoc T, Nakajima S, Kawai KL Indoloditerpenes related to tremorgenic mycotoxin penitrems, from Penicillium crustosum. Phytochemistry 1993 32 1177-1181. Penn J, Swift R, Wigley LJ, Mantle PG, Bilton JN, Sheppard RN Janthitrems B and C, two principal indole-diterpenoids produced by Penicillium janthinellum. Phytochemistry 1993 32 1431-1434. 

Another mycotoxin is patulin, produced by certain species of the moulds Penicillium and Aspergillus, which may grow on apples. There have been occasions when apple juice has been contaminated with patuhn but, provided producers remove infected apples and levels are monitored, there is not normally a danger from exposure (see Chapter 12). 

In this chapter we consider some important fungal metabolites that are biosynthesized by fungi such as Penicillium and Aspergillus species. These include the penicillin and cephalosporin p-lactam antibiotics. Some fungal metabolites derived from amino acids that have achieved notoriety because of their toxicity are described in Chapter 9 on mycotoxins. These include several tryptophan derivatives. Other compounds also derived from amino acids are to be found amongst the fungal pigments described in Chapter 7. 

The amino acid tryptophan is a precursor of several fungal metabolites that affect the central nervous system. We have already met it as a constituent of the ergot alkaloids. Roquefortine (9.25) is a metabolite of Penicillium roqueforti and P. camemberti, which are found on some cheeses. Roquefortine is one of a series of mycotoxins that affect the central nervous system and induce tremors. The more complex penitrems are tremorogenic neurotoxins that are produced by the P. crustosum series. They are biosynthesized from a tryptophan and a triterpene unit. 

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