Next Article in Journal
Organization and ELISA-Based Results of the First Proficiency Testing to Evaluate the Ability of European Union Laboratories to Detect Staphylococcal Enterotoxin Type B (SEB) in Buffer and Milk
Next Article in Special Issue
RNA Sequencing of Contaminated Seeds Reveals the State of the Seed Permissive for Pre-Harvest Aflatoxin Contamination and Points to a Potential Susceptibility Factor
Previous Article in Journal
Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody
Previous Article in Special Issue
Confirmation and Fine Mapping of a Major QTL for Aflatoxin Resistance in Maize Using a Combination of Linkage and Association Mapping
Article Menu
Issue 9 (September) cover image

Export Article

Open AccessArticle
Toxins 2016, 8(9), 267; doi:10.3390/toxins8090267

Bioactivation and Regioselectivity of Pig Cytochrome P450 3A29 towards Aflatoxin B1

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou 510642, China
*
Author to whom correspondence should be addressed.
Academic Editor: Shohei Sakuda
Received: 29 June 2016 / Accepted: 5 September 2016 / Published: 12 September 2016
(This article belongs to the Collection Aflatoxins)
View Full-Text   |   Download PDF [2371 KB, uploaded 12 September 2016]   |  

Abstract

Due to unavoidable contaminations in feedstuff, pigs are easily exposed to aflatoxin B1 (AFB1) and suffer from poisoning, thus the poisoned products potentially affect human health. Heretofore, the metabolic process of AFB1 in pigs remains to be clarified, especially the principal cytochrome P450 oxidases responsible for its activation. In this study, we cloned CYP3A29 from pig liver and expressed it in Escherichia coli, and its activity has been confirmed with the typical P450 CO-reduced spectral characteristic and nifedipine-oxidizing activity. The reconstituted membrane incubation proved that the recombinant CYP3A29 was able to oxidize AFB1 to form AFB1-exo-8,9-epoxide in vitro. The structural basis for the regioselective epoxidation of AFB1 by CYP3A29 was further addressed. The T309A mutation significantly decreased the production of AFBO, whereas F304A exhibited an enhanced activation towards AFB1. In agreement with the mutagenesis study, the molecular docking simulation suggested that Thr309 played a significant role in stabilization of AFB1 binding in the active center through a hydrogen bond. In addition, the bulk phenyl group of Phe304 potentially imposed steric hindrance on the binding of AFB1. Our study demonstrates the bioactivation of pig CYP3A29 towards AFB1 in vitro, and provides the insight for understanding regioselectivity of CYP3A29 to AFB1. View Full-Text
Keywords: cytochrome P450; CYP3A29; AFB1; bioactivation; regioselectivity cytochrome P450; CYP3A29; AFB1; bioactivation; regioselectivity
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Wu, J.; Chen, R.; Zhang, C.; Li, K.; Xu, W.; Wang, L.; Chen, Q.; Mu, P.; Jiang, J.; Wen, J.; Deng, Y. Bioactivation and Regioselectivity of Pig Cytochrome P450 3A29 towards Aflatoxin B1. Toxins 2016, 8, 267.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top