美國科學家最新研究發(fā)現，一種蛋白質能夠生成黃曲霉素,。這是科學家首次發(fā)現黃曲霉素形成的原因。
黃曲霉素是一種毒性極強的劇毒物質,，經常在谷物,、豆類、玉米,、花生和一些干果中檢測到它,，而在濕熱地區(qū)的食品和飼料中出現黃曲霉素的幾率最高。該毒素對人及動物肝臟組織有破壞作用,，嚴重時,，可導致肝癌甚至死亡。
美國加利福尼亞大學歐文分校的研究人員在最新一期《自然》雜志上發(fā)表論文說,，他們研究發(fā)現,，一種名為PT的蛋白質是導致黃曲霉素產生的關鍵物質。研究人員弗蘭克·梅斯肯斯說：“這一發(fā)現將有助于我們了解黃曲霉素究竟是如何引發(fā)人體肝臟癌變的,，同時也將能夠幫助我們開發(fā)出相應的治療藥物,。”（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 461, 1139-1143 (22 October 2009) | doi:10.1038/nature08475
Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization
Jason M. Crawford1,7, Tyler P. Korman4,7, Jason W. Labonte1, Anna L. Vagstad1, Eric A. Hill1, Oliver Kamari-Bidkorpeh5, Shiou-Chuan Tsai4,5,6 & Craig A. Townsend1,2,3
1 Department of Chemistry,
2 Department of Biology,
3 Department of Biophysics, Johns Hopkins University, Maryland 21218, USA
4 Department of Molecular Biology and Biochemistry,
5 Department of Chemistry,
6 Department of Pharmaceutical Sciences, University of California, Irvine, California 92697, USA
7 These authors contributed equally to this work.
Correspondence to: Shiou-Chuan Tsai4,5,6Craig A. Townsend1,2,3 Correspondence and requests for materials should be addressed to C.A.T. or S.-C.T.
Polyketides are a class of natural products with diverse structures and biological activities. The structural variability of aromatic products of fungal nonreducing, multidomain iterative polyketide synthases (NR-PKS group of IPKSs) results from regiospecific cyclizations of reactive poly--keto intermediates1, 2, 3. How poly--keto species are synthesized and stabilized, how their chain lengths are determined, and, in particular, how specific cyclization patterns are controlled have been largely inaccessible and functionally unknown until recently4. A product template (PT) domain is responsible for controlling specific aldol cyclization and aromatization of these mature polyketide precursors, but the mechanistic basis is unknown. Here we present the 1.8 ? crystal structure and mutational studies of a dissected PT monodomain from PksA, the NR-PKS that initiates the biosynthesis of the potent hepatocarcinogen aflatoxin B1 in Aspergillus parasiticus. Despite having minimal sequence similarity to known enzymes, the structure displays a distinct 'double hot dog' (DHD) fold. Co-crystal structures with palmitate or a bicyclic substrate mimic illustrate that PT can bind both linear and bicyclic polyketides. Docking and mutagenesis studies reveal residues important for substrate binding and catalysis, and identify a phosphopantetheine localization channel and a deep two-part interior binding pocket and reaction chamber. Sequence similarity and extensive conservation of active site residues in PT domains suggest that the mechanistic insights gleaned from these studies will prove general for this class of IPKSs, and lay a foundation for defining the molecular rules controlling NR-PKS cyclization specificity.
