Identification of cryptic products of the gliotoxin gene cluster using NMR-based comparative metabolomics and a model for gliotoxin biosynthesis.
Identification of cryptic products of the gliotoxin gene cluster using NMR-based comparative metabolomics and a model for gliotoxin biosynthesis.
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DOI：
10.1021/ja2029987
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发表时间：
2011-06-29
影响因子：
15
通讯作者：
Schroeder, Frank C.
中科院分区：
文献类型：
--
作者：
Forseth, Ry R.;Fox, Ellen M.;Chung, DaWoon;Howlett, Barbara J.;Keller, Nancy P.;Schroeder, Frank C.
胶粘毒素（1）是gli非核糖体肽合成酶（NRPS）基因簇的主要产物，与人类机会致病菌烟曲霉的毒力密切相关。尽管鉴定了gli簇，但胶毒毒素生物合成的途径仍然难以捉摸，部分原因是几乎没有潜在的中间体被鉴定。此外，以前的研究表明，知识的神经胶质依赖性代谢物是不完整的。在这里，我们使用差分分析的2D NMR光谱（DANS）的代谢物提取物来自gli敲除和野生型（WT）菌株，以获得详细的库存gli依赖的代谢物。WT代谢物组与ΔgliZ代谢物组的基于DANS的比较，ΔgliZ是一种缺乏编码gli簇转录调节因子的基因的敲除菌株，揭示了9种新的gliZ依赖性代谢物，包括意想不到的结构基序。它们的鉴定提供了对胶毒素生物合成的深入了解，并可能有助于研究胶毒素簇在A.烟曲霉毒力我们的研究证明了DANS在微生物中相关基因表达和代谢物生物合成方面的实用性。
Gliotoxin (1), a major product of the gli non-ribosomal peptide synthetase (NRPS) gene cluster, is strongly associated with virulence of the opportunistic human pathogen Aspergillus fumigatus. Despite identification of the gli cluster, the pathway of gliotoxin biosynthesis has remained elusive, in part because few potential intermediates have been identified. In addition, previous studies suggest that knowledge of gli-dependent metabolites is incomplete. Here we use differential analysis by 2D NMR spectroscopy (DANS) of metabolite extracts derived from gli knock-out and wild-type (WT) strains to obtain a detailed inventory of gli-dependent metabolites. DANS-based comparison of the WT metabolome with that of ΔgliZ, a knock-out strain devoid of the gene encoding the transcriptional regulator of the gli cluster, revealed nine novel gliZ-dependent metabolites including unexpected structural motifs. Their identification provides insight into gliotoxin biosynthesis and may benefit studies of the role of the gli cluster in A. fumigatus virulence. Our study demonstrates the utility of DANS for correlating gene expression and metabolite biosynthesis in microorganisms.
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影响因子：
3.6
作者：
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作者：
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作者：
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通讯作者：
Carvalho, Ivone
DOI：
10.1073/pnas.0610503104
发表时间：
2007-01-30
影响因子：
11.1
作者：
Butcher, Rebecca A.;Schroeder, Frank C.;Clardy, Jon
通讯作者：
Clardy, Jon