Hydroxyversicolorone: isolation and characterization of a potential intermediate in aflatoxin biosynthesis

Townsend, Craig A.; Plavcan, Kathleen A.; Pal, Kollol; Brobst, Susan W.; Irish, Michael S.; Ely, E. Wesley; Bennett, Joan W.

doi:10.1021/jo00246a015

Cited by 27 publications

(23 citation statements)

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“…Previously (2,25), the molecular masses of VONE and VOROL were reported to be 368 and 370 Da, respectively, suggesting that there is a dihydrofuran ring in the side chain (Fig. 1).…”

Section: Discussionmentioning

confidence: 89%

“…For preparation of VONE and VOROL, the same mutant was cultured for 16 days, and pigments in the mycelia were extracted with acetone and then purified by extraction with ethyl acetate and separation by Daisogel IR-60, Sephadex LH-20, and preparative thin-layer chromatography procedures. The purified VONE and VOROL were identified based on the chemical data obtained from 1 H nuclear magnetic resonance (NMR), mass spectrometry, and infrared analyses, which were compared with previously reported data (2,25).…”

Section: Microorganismsmentioning

confidence: 99%

“…Bennett's group isolated mutant WE-47 (hvn-1) from an aflatoxigenic strain of A. parasiticus by UV irradiation. Townsend et al then determined that this mutant accumulated HVN, VONE, and an alcohol derivative of VONE (25), which we named versicolorol (VOROL). Aflatoxigenic A. parasiticus incorporated [1Ј-…”

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confidence: 99%

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Enzymatic Conversion of Averufin to Hydroxyversicolorone and Elucidation of a Novel Metabolic Grid Involved in Aflatoxin Biosynthesis

Yabe¹,

Chihaya²,

Hamamatsu³

et al. 2003

Appl Environ Microbiol

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The pathway from averufin (AVR) to versiconal hemiacetal acetate (VHA) in aflatoxin biosynthesis was investigated by using cell-free enzyme systems prepared from Aspergillus parasiticus. When (1S,5S)-AVR was incubated with a cell extract of this fungus in the presence of NADPH, versicolorin A and versicolorin B (VB), as well as other aflatoxin pathway intermediates, were formed. When the same substrate was incubated with the microsome fraction and NADPH, hydroxyversicolorone (HVN) and VHA were formed. However, (1R,5R)-AVR did not serve as the substrate. In cell-free experiments performed with the cytosol fraction and NADPH, VHA, versicolorone (VONE), and versiconol acetate (VOAc) were transiently produced from HVN in the early phase, and then VB and versiconol (VOH) accumulated later. Addition of dichlorvos (dimethyl 2,2-dichlorovinylphosphate) to the same reaction mixture caused transient formation of VHA and VONE, followed by accumulation of VOAc, but neither VB nor VOH was formed. When VONE was incubated with the cytosol fraction in the presence of NADPH, VOAc and VOH were newly formed, whereas the conversion of VOAc to VOH was inhibited by dichlorvos. The purified VHA reductase, which was previously reported to catalyze the reaction from VHA to VOAc, also catalyzed conversion of HVN to VONE. Separate feeding experiments performed with A. parasiticus NIAH-26 along with HVN, VONE, and versicolorol (VOROL) demonstrated that each of these substances could serve as a precursor of aflatoxins. Remarkably, we found that VONE and VOROL had ring-opened structures. Their molecular masses were 386 and 388 Da, respectively, which were 18 Da greater than the molecular masses previously reported. These data demonstrated that two kinds of reactions are involved in the pathway from AVR to VHA in aflatoxin biosynthesis: (i) a reaction from (1S,5S)-AVR to HVN, catalyzed by the microsomal enzyme, and (ii) a new metabolic grid, catalyzed by a new cytosol monooxygenase enzyme and the previously reported VHA reductase enzyme, composed of HVN, VONE, VOAc, and VHA. A novel hydrogenation-dehydrogenation reaction between VONE and VOROL was also discovered.

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“…Previously (2,25), the molecular masses of VONE and VOROL were reported to be 368 and 370 Da, respectively, suggesting that there is a dihydrofuran ring in the side chain (Fig. 1).…”

Section: Discussionmentioning

confidence: 89%

Section: Microorganismsmentioning

confidence: 99%

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Enzymatic Conversion of Averufin to Hydroxyversicolorone and Elucidation of a Novel Metabolic Grid Involved in Aflatoxin Biosynthesis

Yabe¹,

Chihaya²,

Hamamatsu³

et al. 2003

Appl Environ Microbiol

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“…Simple redox changes in the hexanoyl side chain yield the internal ketal averufin (4) (22)(23)(24). Oxidation at C-2Ј of 4 induces migration of the anthraquinone nucleus from C-1Ј to C-2Ј to afford hydroxyversicolorone (5) containing the first furan ring (25,26). Preparatory to formation of the second furan ring, oxygen is inserted into the carbon chain of 5 by a proposed Baeyer Villiger-like reaction to give versiconal acetate (6) (27,28).…”

mentioning

confidence: 99%

“…In hemiacetals 5, 6, and 7, the chiral C-2Ј center is benzylic and adjacent to a masked aldehyde. This is an intrinsically labile stereocenter, and each of these three compounds is isolated as a racemate (25,30,31) (Scheme II).…”

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confidence: 99%

Isolation and Characterization of the Versicolorin B Synthase Gene from Aspergillus parasiticus

Silva

Minto

Barry

et al. 1996

Journal of Biological Chemistry

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Versicolorin B synthase catalyzes the side chain cyclization of racemic versiconal hemiacetal (7) to the bisfuran ring system of (؊)-versicolorin B (8), an essential transformation in the aflatoxin biosynthetic pathway of Aspergillus parasiticus. The dihydrobisfuran is key to the mutagenic nature of aflatoxin B 1 (1). The protein, which shows 58% similarity and 38% identity with glucose oxidase from Aspergillus niger, possesses an aminoterminal sequence homologous to the ADP-binding region of other flavoenzymes. However, this enzyme does not require flavin or nicotinamide cofactors for its cyclase activity. The 643-amino acid native enzyme contains three potential sites for N-linked glycosylation, Asn-Xaa-Thr or Asn-Xaa-Ser. The cDNA and genomic clones of versicolorin B synthase were isolated by screening the respective libraries with random-primed DNA probes generated from an exact copy of an internal vbs sequence. This probe was created through polymerase chain reaction by using nondegenerate polymerase chain reaction primers derived from the amino acid sequences of peptide fragments of the enzyme. The 1985-base genomic vbs DNA sequence is interrupted by one intron of 53 nucleotides. Southern blotting, nucleotide sequencing, and detailed restriction mapping of the vbscontaining genomic clones revealed the presence of omtA, a methyltransferase active in the biosynthesis, 3.3 kilobases upstream of vbs and oriented in the opposite direction from vbs. The presence of omtA in close proximity to vbs supports the theory that the genes encoding the aflatoxin biosynthetic enzymes in A. parasiticus are clustered.

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ChemInform Abstract: Hydroxyversicolorone (I)/(II): Isolation and Characterization of a Potential Intermediate in Aflatoxin Biosynthesis.

et al. 1988

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Hydroxyversicolorone: isolation and characterization of a potential intermediate in aflatoxin biosynthesis

Cited by 27 publications

References 0 publications

Enzymatic Conversion of Averufin to Hydroxyversicolorone and Elucidation of a Novel Metabolic Grid Involved in Aflatoxin Biosynthesis

Enzymatic Conversion of Averufin to Hydroxyversicolorone and Elucidation of a Novel Metabolic Grid Involved in Aflatoxin Biosynthesis

Isolation and Characterization of the Versicolorin B Synthase Gene from Aspergillus parasiticus

ChemInform Abstract: Hydroxyversicolorone (I)/(II): Isolation and Characterization of a Potential Intermediate in Aflatoxin Biosynthesis.

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