Isolation and characterization of the citrinin biosynthetic gene cluster from Monascus aurantiacus

Li, Yanping; Xu, Youlong; Huang, Zhibing

doi:10.1007/s10529-011-0745-y

Cited by 62 publications

(45 citation statements)

References 15 publications

(19 reference statements)

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“…The blockage of the citrinin biosynthesis pathway would result in a reduction in citrinin production and an improvement of red pigments. 11,16 However, our results suggested that the biosynthesis of citrinin is independent of that of the pigments because the red pigments did not increase when the ctnB gene was disrupted. One could probably speculate that Monascus does not share enzymes responsible for citrinin biosynthesis and pigment synthesis, despite the same precursor.…”

Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 73%

Lower Citrinin Production by Gene Disruption of ctnB Involved in Citrinin Biosynthesis in Monascus aurantiacus Li AS3.4384

Pan

Zou

et al. 2013

J. Agric. Food Chem.

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The filamentous fungi Monascus spp. have been used in the production of food colorants and health remedies for more than 1000 years in Asia. However, greater attention has been given to the safety of Monascus products because they contain citrinin, which is harmful to the hepatic and renal systems. The citrinin biosynthetic gene cluster has been characterized in Monasucs aurantiacus . The ctnB gene encoding an oxidoreductase is located between pksCT and ctnA. In this study, a ctnB replacement vector (pCTNB-HPH) was constructed to disrupt the ctnB gene with a hygromycin resistance gene as the selection marker. The linear vector was transformed into M. aurantiacus using the protoplast CaCl2/polyethylene glycol (PEG) method. Three ctnB-disrupted strains were obtained by homologous recombination. In comparison to the parental strain, the ΔctnB mutants barely produced citrinin. These data confirmed that the ctnB gene is directly involved in citrinin biosynthesis. Moreover, the yields of the pigments of two disruptants were similar to that of the wild-type strain, but the yield of another mutant was slightly higher than that of the latter strain. These results indicate that the production of the mycotoxin citrinin was successfully eliminated through genetic engineering.

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Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 73%

Lower Citrinin Production by Gene Disruption of ctnB Involved in Citrinin Biosynthesis in Monascus aurantiacus Li AS3.4384

Pan

Zou

et al. 2013

J. Agric. Food Chem.

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“…[21] Overexpression of this pathway (Figure 3b)a lso led to the isolation of the protein tyrosine kinase inhibitors paeciloquinone A( 7 )a nd B( 8 ; Figures S33 and S34), which are shunt products of the biosynthetic pathway of 6 (Scheme S2). [23] The DhdaA strain produced three labdane-related diterpenoid compounds (9-11)a sc haracterized by NMR spectroscopy (Table S14, Figures S35-S44). [23] The DhdaA strain produced three labdane-related diterpenoid compounds (9-11)a sc haracterized by NMR spectroscopy (Table S14, Figures S35-S44).…”

Section: Angewandte Chemiementioning

confidence: 99%

Epigenetic Genome Mining of an Endophytic Fungus Leads to the Pleiotropic Biosynthesis of Natural Products

Mao

et al. 2015

Angewandte Chemie

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The small-molecule biosynthetic potential of most filamentous fungi has remained largely unexplored and represents an attractive source for the discovery of new compounds.G enome sequencing of Calcarisporium arbuscula, am ushroom-endophytic fungus,r evealed 68 core genes that are involved in natural product biosynthesis.T his is in sharp contrast to the predominant production of the ATPase inhibitors aurovertin Ba nd Di nt he wild-type fungus. Inactivation of ah istone H3 deacetylase led to pleiotropic activation and overexpression of more than 75 %o ft he biosynthetic genes.Sampling of the overproduced compounds led to the isolation of ten compounds of which four contained new structures,i ncluding the cyclic peptides arbumycin and arbumelin, the diterpenoid arbuscullic acid A, and the meroterpenoid arbuscullic acid B. Such epigenetic modifications therefore providearapid and global approach to mine the chemical diversity of endophytic fungi.

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“…The gene cluster spanned a 21 kb region containing 6 genes, including pksCT, ctnA genes, containing 10 new genes besides the above 6 genes, but the functions of only a few genes have been analyzed and predicted, and most genes in the citrinin biosynthetic gene cluster are still not investigated (Li et al 2012). Therefore, it still needs so much effort to study the biosynthesis pathway of citrinin.…”

Section: Introductionmentioning

confidence: 99%

ThectnGgene encodes carbonic anhydrase involved in mycotoxin citrinin biosynthesis fromMonascus aurantiacus

Xiao

et al. 2014

Food Additives & Contaminants: Part A

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Citrinin, a fungal secondary metabolite of polyketide origin, is moderately nephrotoxic to vertebrates, including humans. Citrinin is synthesised by condensation of acetyl-CoA and malonyl-CoA. Six genes involved in the citrinin biosynthesis, including pksCT, ctnA and ctnB, have been cloned in Monascus purpureus. The pksCT gene encodes a polyketide synthase; ctnA is a regulatory factor; and ctnB encodes an oxidoreductase. When the three genes were respectively disrupted, the disruption strains drastically decreased citrinin production or barely produced citrinin. Ten new genes have been discovered in Monascus aurantiacus besides the above six genes. One of these gene displayed the highest similarity to the β-carbonic anhydrase gene from Aspergillus oryzae (74% similarity) and was designated ctnG. To learn more about the citrinin biosynthetic pathway, a ctnG-replacement vector was constructed to disrupt ctnG with the hygromycin resistance gene as the selection marker, then transformed into M. aurantiacus Li AS3.4384 by a protoplast-PEG method. The citrinin content of three disruptants was reduced to about 50%, meanwhile pigment production decreased by 23%, respectively, over those of the wild-type strains. ctnG was deduced to be involved in the formation of malonyl-CoA as a common precursor of red pigments and citrinin. Therefore, the disruption of the ctnG gene decreased citrinin and pigment production. M. aurantiacus Li AS3.4384 can produce higher concentrations of citrinin than other strains such as M. purpureus and M. ruber. Establishing the function of citrinin biosynthetic genes in M. aurantiacus is helpful in understanding the citrinin synthetic pathway and adopting some strategies to control contamination.

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Isolation and characterization of the citrinin biosynthetic gene cluster from Monascus aurantiacus

Cited by 62 publications

References 15 publications

Lower Citrinin Production by Gene Disruption of ctnB Involved in Citrinin Biosynthesis in Monascus aurantiacus Li AS3.4384

Lower Citrinin Production by Gene Disruption of ctnB Involved in Citrinin Biosynthesis in Monascus aurantiacus Li AS3.4384

Epigenetic Genome Mining of an Endophytic Fungus Leads to the Pleiotropic Biosynthesis of Natural Products

ThectnGgene encodes carbonic anhydrase involved in mycotoxin citrinin biosynthesis fromMonascus aurantiacus

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