Biosynthesis of citrinin in aspergillus terreus.

Citrinin produced by Aspergillus, Penicillium, and Monascus species is a polyketide compound that has nephrotoxic activity in mammals and is bactericidal toward gram-positive bacteria. To avoid the risk of citrinin contamination in other fermentation products produced by Monascus purpureus, knowledge of the citrinin biosynthetic genes is needed so that citrinin-nonproducing strains can be generated. We cloned a polyketide synthase (PKS) gene from M. purpureus with degenerate primers designed to amplify the conserved region of a ketosynthase domain of a fungal PKS. A 13-kb genomic DNA fragment was identified that contained a full-length PKS gene (pksCT) of 7,838 bp with a single 56-bp intron. pksCT encodes a 2,593-amino-acid protein that contains putative domains for ketosynthase, acyltransferase, acyl carrier protein (ACP), and a rare methyltransferase. There was no obvious thioesterase domain, which usually is downstream of the ACP domain in multi-aromatic-ring PKSs. pksCT transcription was correlated with citrinin production, suggesting that the pksCT gene product was involved in citrinin biosynthesis. Homologous recombination between the wild-type allele and a truncated disruption construct resulted in a pksCT-disrupted strain of M. purpureus. The disruptant did not produce citrinin, but a pksCT revertant generated by successive endogenous recombination events in the pksCT disruptant restored citrinin production, indicating that pksCT encoded the PKS responsible for citrinin biosynthesis in M. purpureus.

Biosynthesis of citrinin in Aspergillus terreus.

of citrinin in Aspergillus terreus.

Biosynthetic Pathway of Citrinin in the Filamentous …

The selective effect of various levels of phosphate and nitrate (as fertilizers) on biosynthesis of aflatoxin byAspergillus parasiticus var.globosus, and citrinin byA. terreus var.aureus was studied in defined culture medium. Phosphate at 35–175 mmol per 50 mL decreased aflatoxin production, but increased citrinin synthesis. Nitrate at 73–365 mmol per 50 mL stimulated the synthesis of aflatoxin but depressed that of citrinin. A rise in the levels of nitrate and phosphate led to a decrease in aflatoxin production, an increase in citrinin production and an accumulation of mycelial phosphate and nitrate contents.

The Biosynthesis of Citrinin in Penicillium citrinum

A. terreus is an especially prolific producer of secondary metabolites. A few of the compounds that are produced by A. terreus are aspulvinone (), asterric acid (), asterriquinone (), butyrolactone I (), citrinin (), emodin (), geodin (), itaconate (), lovastatin (, ), questrin (), sulochrin (), and terrecyclic acid (). Lovastatin, also known as mevinolin or monacolin K, is clinically useful for reducing serum cholesterol () and slowing the progression of atherosclerosis (). Lovastatin and related compounds inhibit cholesterol synthesis by inhibiting the rate-limiting step in cellular cholesterol biosynthesis, namely, the conversion of hydroxymethylglutaryl coenzyme A to mevalonic acid by 3-hydroxy-3-methylglutaryl-coenzyme A reductase. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, such as lovastatin, reversibly inhibit cell proliferation by inducing a block in the G1 phase of the cell cycle in a wide variety of normal and tumorigenic mammalian cell lines (, ).

Culture-based and sequence-based insights into biosynthesis of secondary metabolites by Aspergillus terreus ATCC 20542
Culture-based and sequence-based insights into biosynthesis of secondary metabolites by Aspergillus terreus ..

in the catalyzing steps in cholesterol biosynthesis.

Aspergillus terreus is an outstanding producer of many bioactive agents, ..

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speculated that ATEG_03432 was responsible for the biosynthesis of citrinin in A

from a blocked mutant of Aspergillus terreus allows ..