Abstract

The aflatoxins are a family of carcinogenic mycotoxins of polyketide origin. Aflatoxin B1 is the most potent liver carcinogen known for the laboratory rat. These toxins occur widely in many parts of the world as food contaminants and are an important environmental health hazard. The biosynthesis of this family of toxins is to be investigated using specific 2H/13C-, 3H/14C- and 13C/180-labeled specimens of averufin, nidurufin, 6-deoxyversicolorin A and potential ortho-carboxybenzophenone and dienone intermediates in the bisfuran and xanthone rearrangement steps. These experiments will establish unequivocally the fate of isotopically-labeled centers by Ft-nmr or degradation. Mechanistic and stereochemical information will be sought in these experiments and biomimetic syntheses will be attempted to explain the in vitro chemistry of certain reactive systems.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES001670-09
Application #
3249581
Study Section
(SSS)
Project Start
1978-02-01
Project End
1987-01-31
Budget Start
1986-02-01
Budget End
1987-01-31
Support Year
9
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
Schools of Arts and Sciences
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Saraiva, Raúl G; Huitt-Roehl, Callie R; Tripathi, Abhai et al. (2018) Chromobacterium spp. mediate their anti-Plasmodium activity through secretion of the histone deacetylase inhibitor romidepsin. Sci Rep 8:6176
Herbst, Dominik A; Huitt-Roehl, Callie R; Jakob, Roman P et al. (2018) The structural organization of substrate loading in iterative polyketide synthases. Nat Chem Biol 14:474-479
Herbst, Dominik A; Townsend, Craig A; Maier, Timm (2018) The architectures of iterative type I PKS and FAS. Nat Prod Rep 35:1046-1069
de Jonge, Ronnie; Ebert, Malaika K; Huitt-Roehl, Callie R et al. (2018) Gene cluster conservation provides insight into cercosporin biosynthesis and extends production to the genus Colletotrichum. Proc Natl Acad Sci U S A 115:E5459-E5466
Cohen, Douglas R; Townsend, Craig A (2018) Characterization of an Anthracene Intermediate in Dynemicin Biosynthesis. Angew Chem Int Ed Engl 57:5650-5654
Cohen, Douglas R; Townsend, Craig A (2018) A dual role for a polyketide synthase in dynemicin enediyne and anthraquinone biosynthesis. Nat Chem 10:231-236
Storm, Philip A; Townsend, Craig A (2017) In trans hydrolysis of carrier protein-bound acyl intermediates by CitA during citrinin biosynthesis. Chem Commun (Camb) 54:50-53
Barajas, Jesus F; Shakya, Gaurav; Moreno, Gabriel et al. (2017) Polyketide mimetics yield structural and mechanistic insights into product template domain function in nonreducing polyketide synthases. Proc Natl Acad Sci U S A 114:E4142-E4148
Storm, Philip A; Herbst, Dominik A; Maier, Timm et al. (2017) Functional and Structural Analysis of Programmed C-Methylation in the Biosynthesis of the Fungal Polyketide Citrinin. Cell Chem Biol 24:316-325
Zhou, Jiawang; Outlaw, Victor K; Townsend, Craig A et al. (2016) Quenching of pH-Responsive Luminescence of a Benzoindolizine Sensor by an Ultrafast Hydrogen Shift. Chemistry 22:15212-15215

Showing the most recent 10 out of 53 publications