美国科学家最新研究发现，一种蛋白质能够生成黄曲霉素。这是科学家首次发现黄曲霉素形成的原因。
黄曲霉素是一种毒性极强的剧毒物质，经常在谷物、豆类、玉米、花生和一些干果中检测到它，而在湿热地区的食品和饲料中出现黄曲霉素的几率最高。该毒素对人及动物肝脏组织有破坏作用，严重时，可导致肝癌甚至死亡。
美国加利福尼亚大学欧文分校的研究人员在最新一期《自然》杂志上发表论文说，他们研究发现，一种名为PT的蛋白质是导致黄曲霉素产生的关键物质。研究人员弗兰克·梅斯肯斯说：“这一发现将有助于我们了解黄曲霉素究竟是如何引发人体肝脏癌变的，同时也将能够帮助我们开发出相应的治疗药物。”（生物谷Bioon.com）
生物谷推荐原始出处：
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.
