Penicillium citrinum

A series of hypocholesteremic agents were isolated from Monascus and named monacolin J, K, and L. These polyketides were first isolated from cultures of Penicillium citrinum and they can inhibit specifically the enzyme controlling the rate of cholesterol biosynthesis. They are currently used in China in traditional and modem medicine. 

Enzymes PPL, lipase from Pseudomonas fluorescens F-AP, lipase from Rhizopus orizae AP-6, lipase from Aspergillus niger, SP-254, lipase from Aspergillus oryzae P-2, Chirazyme WCPC, whole cell cultures of Penicillium citrinum WCPFL, whole cell cultures of Pseudomona fluorescens CAL-B, lipase from Candida antarctica B PS-C, lipase from Pseudomonas cepacia GCL, lipase from Geotrichum candidum. n.r. not reported. 

While having three metal ions in an enzyme active site is uncommon, it is not unique to PLCBc. The well-known alkaline phosphatase from E. coli (APase) contains two zinc ions and a magnesium ion [67], whereas the a-toxin from Clostridiumperfringens [68]. and the PI nuclease from Penicillium citrinum [69] each contain three zinc ions. Indeed, the zinc ions and coordinating ligands of PI nuclease bear an uncanny resemblance to those of PLCBc as the only differ-... 

Fig. 23.— 13C-N.m.r. Spectra of the /3-D-( 1—>5)-Linked D-Galactofuranan (A) Obtained by Hydrolysis of Its Malonic Ester (B), Produced by Penicillium citrinum Thom 1131. (Solvent, D20 temperature, ambient chemical shifts expressed as 8C, relative to external tetramethylsilane.)...

The ACS function is known only in higher plants. The activity of ACS isozymes is a key regulatory factor of ethylene biosynthesis pathway. In general, microorganisms liberate ethylene but their ethylene synthesis pathways do not involve ACC as an intermediate. Penicillium citrinum is the first reported microorganism that is able to synthesize ACC from SAM and to degrade it into ammonia and a-ketobutyrate, not to ethylene. ACS from P. citrinum shows a 100-fold higher for SAM than its plant counterparts. ... 

Lovastatin and mevastatin Lovastatin, (lS,3R,7S,8S,8aR)-l,2,3,7,8,8a-hexahydro-3, 7-dimethyl-8-[-[2R,4R]-[tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl]ethyl]-l-naphthyl (S)-2-methylbutyrate (20.2.7) is isolated from Monascus rubber [17] mA Aspergillus terreus [18], as is mevastatin (lS,3R,7S,8S,8aR)-l,2,3,7,8, 8a-hexahydro-7-metliyl-8-[-(2R,4R)-[tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl]ethyl]-l-naphthyl (S)-2-metliylbutyrate (20.2.8), which is isolated from Penicillium citrinum [19, 20] as well as from Penicillium brevicom-pactum [21]. 

Lovastatin and mevastatin are new-generation drugs that were introduced into medicine for treating hyperlipocholesterolemia, and they are unique compounds. Lovastatin is isolated from Aspergillus terreus mushrooms. Mevastatin is a chemically analogous compound that differs only in the absence of a methyl group at C3 of the naphthaline system, and it is isolated from Penicillium citrinum mushrooms. 

Y. D. Lobsanov, F. Vallee, A. Imberty, T. Yoshida, P. Yip, A. Herscovics, and P. L. Howell, Structure of Penicillium citrinum al,2-mannosidase reveals the basis for differences in specificity of the endoplasmatic reticulum and golgi class I enzymes, J. Biol. Chem., 277 (2002) 5620-5630. 

Sasaki, M., Tsuda, M., Sekiguchi, M., Mikami, Y. and Kobayashi, J. 2005. Peri-nadine A, a novel tetracyclic alkaloid from marine-derived fungus Penicillium citrinum. Organic Letters, 1 4261 264. 

Liebminger S, Eberl A, Sousa E et al (2007) Hydrolysis of PET and bis-(benzoyloxyethyl) terephthalate with a new polyesterase from Penicillium citrinum. Biocatal Biotrans 25 171-177... 

Penicillium citrinum Thom (1910), Eumyc./anti-cholesterolemic... 

Endo, A., Kuroda, M., and Tsujita, Y., ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinum. J. Antibiot., 29, 1346, 1976. 

Abdel-Fattah, A. F. and EL-Hawwary, N. M. 1972. Purification and proteolytic action of milk-clotting enzyme produced by Penicillium citrinum. J. Gen. Appl. Microbiol... 

Pravastatin (47) and Mevastatin (48) are anticholesterol drugs which act by competitively inhibiting HMG Co A reductase [75], Pravastatin sodium is produced by two fermentation steps. The first step is the production of compound ML-236B by Penicillium citrinum [75-77], The purified compound was con-... 

Matsumoto, K., Yamaguchi, M., and Ichishima, E. (1994). Molecular cloning and nucleotide sequence of the complementary DNA for penicillolysin gene, plnC, an 18 kDa metalloendopeptidase gene from Penicillium citrinum. Biochim. Biophys. Acta, 1218, 469-472. 

Yoshida, T., Inoue, T., and Ichishima, E. (1993). 1,2-a-D-mannosidase from Penicillium citrinum molecular and enzymatic properties of two isoenzymes. Biochem. J., 290, 349-354. 

Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase is the rate-limiting enzyme in the cholesterol biosynthetic pathway (Fig. 1). In contrast to desmosterol and other late-stage lipid-soluble intermediates, HMG is water-soluble, and there are alternative metabolic pathways for its breakdown when HMG-CoA reductase is inhibited so that there is no buildup of potentially toxic precursors. Therefore, of the more than 30 enzymes involved in the biosynthesis of cholesterol, HMG-CoA reductase was a natural target. Substances that have a powerful inhibitory effect on this enzyme, including ML236B (compactin), were first discovered by Endo in a fermentation broth of Penicillium citrinum in the... 

Pravastatin (10) is another HMG-CoA reductase for the inhibition of cholesterol biosynthesis it is marketed by Sanyo and Bristol Myers Squibb under the trade names Mevalotin and Pravachol.87 It has a close structural relationship to lovastatin and simvastatin. It is produced by a two-step sequence. First, mevastatin (11), also known as ML-236B or compactin, is prepared by fermentation of Penicillium citrinum ss it is then enzymatically hydroxylated to produce 11 (Scheme 31.7).88-101... 

Research groups in Japan [1] have screened over 8000 microbial extracts for their ability to produce an inhibitor of sterol synthesis in vitro. These studies led to the isolation of mevastatin from cultures of Penicillium citrinum. Mevastatin (Fig. 4.2) served as the lead-molecule for seven statins which currently are among the best-selling drugs. 

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