Biosynthesis and Role in Virulence of the Histone Deacetylase Inhibitor Depudecin from Alternaria brassicicola

Biosynthesis and Role in Virulence of the Histone Deacetylase Inhibitor Depudecin from Alternaria brassicicola
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DOI:
10.1094/mpmi-22-10-1258
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发表时间:
2009-10-01
影响因子:
3.5
通讯作者:
Walton, Jonathan D.
Walton, Jonathan D.
中科院分区:
生物学2区
文献类型:
--
作者:
Wight, Wanessa D.;Kim, Kwang-Hyung;Walton, Jonathan D.

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Depudecin是一种由病原真菌芸苔链格孢(Alternaria brassicicicola)产生的11个碳的线性聚酮化合物,是组蛋白脱乙酰酶(HDAC)的抑制剂。化学上无关的HDAC抑制剂,HC毒素,早期被证明是一个主要的毒力因子之间的相互作用Cochliobolus carbonum和它的主机,玉米。为了验证depudecin是否也是A.在芸苔属中,我们鉴定了depudecin生物合成的基因,并产生了depudecin缺失突变体。depudecin基因簇包含六个基因(DEP 1至DEP 6),其被预测编码聚酮合酶(AbPKS 9或DEP 5)、转录因子(DEP 6)、两种单加氧酶(DEP 2和DEP 4)、主要易化剂超家族的转运蛋白(DEP 3)和一种未知功能的蛋白(DEP 1)。通过靶向基因破坏证实了参与DEP 2、DEP 4、DEP 5和DEP 6的depudecin生产。DEP 6是DEP 1至DEP 5表达所需的,但不是直接侧翼基因,因此定义了共调节的depudecin生物合成簇。在相关真菌Stagonospora nodorum和Pyrenophora tritici-repentis中,depudecin基因簇侧翼的基因而不是簇本身以相同的顺序保守。Depudecin减突变体具有小的(10%),但统计学上显着降低对卷心菜(甘蓝)的毒力,但不是对拟南芥。因此,depudecin在毒力中的作用不如HC毒素显著。
Depudecin, an eleven-carbon linear polyketide made by the pathogenic fungus Alternaria brassicicola, is an inhibitor of histone deacetylase (HDAC). A chemically unrelated HDAC inhibitor, HC toxin, was earlier shown to be a major virulence factor in the interaction between Cochliobolus carbonum and its host, maize. In order to test whether depudecin is also a virulence factor for A. brassicicola, we identified the genes for depudecin biosynthesis and created depudecin-minus mutants. The depudecin gene cluster contains six genes (DEP1 to DEP6), which are predicted to encode a polyketide synthase (AbPKS9 or DEP5), a transcription factor (DEP6), two monooxygenases (DEP2 and DEP4), a transporter of the major facilitator superfamily (DEP3), and one protein of unknown function (DEP1). The involvement in depudecin production of DEP2, DEP4, DEP5, and DEP6 was demonstrated by targeted gene disruption. DEP6 is required for expression of DEP1 through DEP5 but not the immediate flanking genes, thus defining a coregulated depudecin biosynthetic cluster. The genes flanking the depudecin gene cluster but not the cluster itself are conserved in the same order in the related fungi Stagonospora nodorum and Pyrenophora tritici-repentis. Depudecin-minus mutants have a small (10%) but statistically significant reduction in virulence on cabbage (Brassica oleracea) but not on Arabidopsis. The role of depudecin in virulence is, therefore, less dramatic than that of HC toxin.