The fumagillin gene cluster, an example of hundreds of genes under veA control in Aspergillus fumigatus.
The fumagillin gene cluster, an example of hundreds of genes under veA control in Aspergillus fumigatus.
复制标题
DOI：
10.1371/journal.pone.0077147
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Calvo AM
中科院分区：
文献类型：
--
作者：
Dhingra S;Lind AL;Lin HC;Tang Y;Rokas A;Calvo AM
烟曲霉是侵袭性曲霉病的病原体，导致免疫功能低下患者感染相关的死亡率。我们以前表明，保守的和独特的真菌veA基因影响不同的细胞过程，如形态发育，胶凝毒素生物合成和蛋白酶活性，这表明这种医学相关的真菌的基因组的全球监管作用。在这项研究中，RNA测序分析显示veA控制着A中数百个基因的表达。烟曲霉，包括那些包含十几个已知的次级代谢物基因簇。化学分析证实，除了胶毒毒素，veA还控制该生物体中其他次级代谢产物的合成。在由veA调节的次级代谢物基因簇中，有一个难以捉摸但最近鉴定的基因簇负责烟曲霉素的生物合成，烟曲霉素是一种已知通过与人甲硫氨酸氨基肽酶2结合而具有抗血管生成活性的部分萜类化合物。烟曲霉素基因簇包含一个veA依赖的调控基因fumR（Afu8g00420），编码一个假定的C6型转录因子。fumR的缺失导致基因簇的沉默和烟曲霉素生物合成的消除。我们发现fumR的表达也依赖于laeA，这是一种编码真菌天鹅绒复合物另一种成分的基因。本研究的结果表明，veA是一个全局调节剂的次级代谢在A。veA可能是化学发育与形态发育和其它细胞过程耦合通道。
Aspergillus fumigatus is the causative agent of invasive aspergillosis, leading to infection-related mortality in immunocompromised patients. We previously showed that the conserved and unique-to-fungi veA gene affects different cell processes such as morphological development, gliotoxin biosynthesis and protease activity, suggesting a global regulatory effect on the genome of this medically relevant fungus. In this study, RNA sequencing analysis revealed that veA controls the expression of hundreds of genes in A. fumigatus, including those comprising more than a dozen known secondary metabolite gene clusters. Chemical analysis confirmed that veA controls the synthesis of other secondary metabolites in this organism in addition to gliotoxin. Among the secondary metabolite gene clusters regulated by veA is the elusive but recently identified gene cluster responsible for the biosynthesis of fumagillin, a meroterpenoid known for its anti-angiogenic activity by binding to human methionine aminopeptidase 2. The fumagillin gene cluster contains a veA-dependent regulatory gene, fumR (Afu8g00420), encoding a putative C6 type transcription factor. Deletion of fumR results in silencing of the gene cluster and elimination of fumagillin biosynthesis. We found expression of fumR to also be dependent on laeA, a gene encoding another component of the fungal velvet complex. The results in this study argue that veA is a global regulator of secondary metabolism in A. fumigatus, and that veA may be a conduit via which chemical development is coupled to morphological development and other cellular processes.
登录
查看更多内容
影响因子：
--
作者：
Dhingra, Sourabh;Andes, David;Calvo, Ana M.
通讯作者：
Calvo, Ana M.
影响因子：
3.1
作者：
AMITANI, R;TAYLOR, G;WILSON, R
通讯作者：
WILSON, R
影响因子：
3.6
作者：
Fernandes, M;Keller, NP;Adams, TH
通讯作者：
Adams, TH
影响因子：
4.4
作者：
Calvo, AM;Bok, J;Keller, NP
通讯作者：
Keller, NP
影响因子：
--
作者：
Gibbons, John G.;Beauvais, Anne;Rokas, Antonis
通讯作者：
Rokas, Antonis