Transcription Factor Repurposing Offers Insights into Evolution of Biosynthetic Gene Cluster Regulation.
Transcription Factor Repurposing Offers Insights into Evolution of Biosynthetic Gene Cluster Regulation.
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转录因子的重新利用为生物合成基因簇调控的进化提供了见解。
DOI：
10.1128/mbio.01399-21
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发表时间：
2021-08-31
期刊：
影响因子：
6.4
通讯作者：
Keller NP
中科院分区：
文献类型：
--
作者：
Wang W;Drott M;Greco C;Luciano-Rosario D;Wang P;Keller NP
真菌王国为我们鉴定生物合成基因簇（BGC）和研究BGC的基因组成如何在物种和属间进化的能力提供了进步。然而，很少有人知道特定的BGC调节器，介导如何BGC产生次级代谢产物（SM）的演变。对烟曲霉黄青霉素BGC的生物信息学研究揭示了黄曲霉黄青霉素BGC在散囊藻目物种中的进化轨迹。虽然关键的调控和酶基因在扩展青霉中是保守的，但与AfXanC在A.烟熏。令人惊讶的是，OE：：PexanC反而被发现通过cit途径特异性TF（ctnA）的反式诱导促进扩展毕赤酵母中的桔霉素合成，如通过cit BGC表达和ctnA缺失和OE：：PexanC单突变体和双突变体的化学分析所确定的。OE：：AfxanC导致A中xan基因表达和代谢物合成的显著增加。但对扩展青霉中黄青霉素或桔霉素的产生没有影响。通过生物信息学和启动子突变分析，在A.烟曲霉xan BGC基因。该基序不在ctnA启动子中，表明PeXanC的不同结合位点。XanC直系同源物的生物信息学检查汇编以及多种曲霉属和青霉属中Xan BGC中5′-AGTCAGCA-3′结合基序的存在/不存在。支持XanC调控目标的进化分歧，我们推测这反映了Eurotiales中的exaptation事件。
The fungal kingdom has provided advances in our ability to identify biosynthetic gene clusters (BGCs) and to examine how gene composition of BGCs evolves across species and genera. However, little is known about the evolution of specific BGC regulators that mediate how BGCs produce secondary metabolites (SMs). A bioinformatics search for conservation of the Aspergillus fumigatus xanthocillin BGC revealed an evolutionary trail of xan-like BGCs across Eurotiales species. Although the critical regulatory and enzymatic genes were conserved in Penicillium expansum, overexpression (OE) of the conserved xan BGC transcription factor (TF) gene, PexanC, failed to activate the putative xan BGC transcription or xanthocillin production in P. expansum, in contrast to the role of AfXanC in A. fumigatus. Surprisingly, OE::PexanC was instead found to promote citrinin synthesis in P. expansum via trans induction of the cit pathway-specific TF, ctnA, as determined by cit BGC expression and chemical profiling of ctnA deletion and OE::PexanC single and double mutants. OE::AfxanC results in significant increases of xan gene expression and metabolite synthesis in A. fumigatus but had no effect on either xanthocillin or citrinin production in P. expansum. Bioinformatics and promoter mutation analysis led to the identification of an AfXanC binding site, 5′-AGTCAGCA-3′, in promoter regions of the A. fumigatus xan BGC genes. This motif was not in the ctnA promoter, suggesting a different binding site of PeXanC. A compilation of a bioinformatics examination of XanC orthologs and the presence/absence of the 5′-AGTCAGCA-3′ binding motif in xan BGCs in multiple Aspergillus and Penicillium spp. supports an evolutionary divergence of XanC regulatory targets that we speculate reflects an exaptation event in the Eurotiales.