Production of M-/GM-group aflatoxins catalyzed by the OrdA enzyme in aflatoxin biosynthesis

Yabe, Kimiko; Chihaya, Naomi; Hatabayashi, Hidemi; Kito, Masako; Hoshino, Satoshi; Zeng, Hongmei; Cai, Jingjing; Nakajima, Hiromitsu

doi:10.1016/j.fgb.2012.06.011

Cited by 36 publications

(40 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The only remaining unassigned oxygenase in the gene cluster was therefore the P450 gene, Af 510, which shows the strongest sequence homology to the multifunctional P450 OrdA 18 in aflatoxin biosynthesis (47% protein identity). Wiemann et al reported that deletion of Af 510 in A. fumigatus led to no detectable accumulation of any intermediates.…”

Section: Resultsmentioning

confidence: 99%

Generation of Complexity in Fungal Terpene Biosynthesis: Discovery of a Multifunctional Cytochrome P450 in the Fumagillin Pathway

Lin¹,

Tsunematsu

Dhingra

et al. 2014

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Fumagillin (1), a meroterpenoid from Aspergillus fumigatus, is known for its antiangiogenic activity due to binding to human methionine aminopeptidase 2. 1 has a highly oxygenated structure containing a penta-substituted cyclohexane that is generated by oxidative cleavage of the bicyclic sesquiterpene β-trans-bergamotene. The chemical nature, order, and biochemical mechanism of all the oxygenative tailoring reactions has remained enigmatic despite the identification of the biosynthetic gene cluster and the use of targeted-gene deletion experiments. Here, we report the identification and characterization of three oxygenases from the fumagillin biosynthetic pathway, including a multifunctional cytochrome P450 monooxygenase, a hydroxylating nonheme-iron-dependent dioxygenase, and an ABM family monooxygenase for oxidative cleavage of the polyketide moiety. Most significantly, the P450 monooxygenase is shown to catalyze successive hydroxylation, bicyclic ring-opening, and two epoxidations that generate the sesquiterpenoid core skeleton of 1. We also characterized a truncated polyketide synthase with a ketoreductase function that controls the configuration at C-5 of hydroxylated intermediates.

show abstract

Section: Resultsmentioning

confidence: 99%

Generation of Complexity in Fungal Terpene Biosynthesis: Discovery of a Multifunctional Cytochrome P450 in the Fumagillin Pathway

Lin¹,

Tsunematsu

Dhingra

et al. 2014

J. Am. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…After entering the mammaliam body (human or animals), aflatoxins are metabolized by the liver cytochrome P450 enzymes to a reactive epoxide intermediate which becomes more carcinogenic, or be hydroxylated and become the less harmful aflatoxins M 1 and M 2 . However, recent studies by feeding with aspertoxin (12c-hydroxy-OMST) [166] indicated that A. parasiticus produces the minor aflatoxins M 1 (AFM 1 ), M 2 (AFM 2 ), GM 1 (AFGM 1 ), and GM 2 (AFGM 2 ), as well as the major aflatoxins B 1 (AFB 1 ), B 2 (AFB 2 ), G 1 (AFG 1 ), and G 2 (AFG 2 ). It demonstrated that aspertoxin is a precursor of AFM 1 and AFGM 1 .…”

Section: Genetics and Molecular Biology Of Aflatoxin Biosynthesismentioning

confidence: 99%

Current Understanding on Aflatoxin Biosynthesis and Future Perspective in Reducing Aflatoxin Contamination

2012

Toxins

282

248

View full text Add to dashboard Cite

Traditional molecular techniques have been used in research in discovering the genes and enzymes that are involved in aflatoxin formation and genetic regulation. We cloned most, if not all, of the aflatoxin pathway genes. A consensus gene cluster for aflatoxin biosynthesis was discovered in 2005. The factors that affect aflatoxin formation have been studied. In this report, the author summarized the current status of research progress and future possibilities that may be used for solving aflatoxin contamination.

show abstract

“…AF is synthesized by particular Aspergillus species, including A. flavus , A. parasiticus , A. nomius , and A. bombysis . Genetic investigations of the AF synthetic mechanism have shown AF synthetic fungi contain a specific gene cluster [1,2,3,4,5,6,7,8,9]. However, many non-toxigenic strains also have this gene cluster, although these clusters may have partial deletions and/or substitutions compared to those in AF synthetic fungi.…”

Section: Introductionmentioning

confidence: 99%

Addition of Carbon to the Culture Medium Improves the Detection Efficiency of Aflatoxin Synthetic Fungi

Suzuki

Iwahashi

2016

Toxins

View full text Add to dashboard Cite

Aflatoxin (AF) is a harmful secondary metabolite that is synthesized by the Aspergillus species. Although AF detection techniques have been developed, techniques for detection of AF synthetic fungi are still required. Techniques such as plate culture methods are continually being modified for this purpose. However, plate culture methods require refinement because they suffer from several issues. In this study, activated charcoal powder (carbon) was added to a culture medium containing cyclodextrin (CD) to enhance the contrast of fluorescence and improve the detection efficiency for AF synthetic fungi. Two culture media, potato dextrose agar and yeast extract sucrose agar, were investigated using both plate and liquid cultures. The final concentrations of CD and carbon in the media were 3 mg/mL and 0.3 mg/mL, respectively. Addition of carbon improved the visibility of fluorescence by attenuating approximately 30% of light scattering. Several fungi that could not be detected with only CD in the medium were detected with carbon addition. The carbon also facilitated fungal growth in the potato dextrose liquid medium. The results suggest that addition of carbon to media can enhance the observation of AF-derived fluorescence.

show abstract

Production of M-/GM-group aflatoxins catalyzed by the OrdA enzyme in aflatoxin biosynthesis

Cited by 36 publications

References 32 publications

Generation of Complexity in Fungal Terpene Biosynthesis: Discovery of a Multifunctional Cytochrome P450 in the Fumagillin Pathway

Generation of Complexity in Fungal Terpene Biosynthesis: Discovery of a Multifunctional Cytochrome P450 in the Fumagillin Pathway

Current Understanding on Aflatoxin Biosynthesis and Future Perspective in Reducing Aflatoxin Contamination

Addition of Carbon to the Culture Medium Improves the Detection Efficiency of Aflatoxin Synthetic Fungi

Contact Info

Product

Resources

About