Niu Jing, Alazi Ebru, Reid Ian D, Arentshorst Mark, Punt Peter J, Visser Jaap, Tsang Adrian, Ram Arthur F J
Molecular Microbiology and Biotechnology, Leiden University, Institute of Biology Leiden, 2333 BE Leiden, The Netherlands.
Centre for Structural and Functional Genomics, Concordia University, Montreal, Quebec H4B1R6, Canada.
Genetics. 2017 Jan;205(1):169-183. doi: 10.1534/genetics.116.194050. Epub 2016 Nov 9.
The expression of genes encoding extracellular polymer-degrading enzymes and the metabolic pathways required for carbon utilization in fungi are tightly controlled. The control is mediated by transcription factors that are activated by the presence of specific inducers, which are often monomers or monomeric derivatives of the polymers. A D-galacturonic acid-specific transcription factor named GaaR was recently identified and shown to be an activator for the expression of genes involved in galacturonic acid utilization in Botrytis cinerea and Aspergillus niger Using a forward genetic screen, we isolated A. niger mutants that constitutively express GaaR-controlled genes. Reasoning that mutations in the gaaR gene would lead to a constitutively activated transcription factor, the gaaR gene in 11 of the constitutive mutants was sequenced, but no mutations in gaaR were found. Full genome sequencing of five constitutive mutants revealed allelic mutations in one particular gene encoding a previously uncharacterized protein (NRRL3_08194). The protein encoded by NRRL3_08194 shows homology to the repressor of the quinate utilization pathway identified previously in Neurospora crassa (qa-1S) and Aspergillus nidulans (QutR). Deletion of NRRL3_08194 in combination with RNA-seq analysis showed that the NRRL3_08194 deletion mutant constitutively expresses genes involved in galacturonic acid utilization. Interestingly, NRRL3_08194 is located next to gaaR (NRRL3_08195) in the genome. The homology to the quinate repressor, the chromosomal clustering, and the constitutive phenotype of the isolated mutants suggest that NRRL3_08194 is likely to encode a repressor, which we name GaaX. The GaaR-GaaX module and its chromosomal organization is conserved among ascomycetes filamentous fungi, resembling the quinate utilization activator-repressor module in amino acid sequence and chromosomal organization.
真菌中编码细胞外聚合物降解酶的基因表达以及碳利用所需的代谢途径受到严格控制。这种控制由转录因子介导,这些转录因子被特定诱导物激活,而这些诱导物通常是聚合物的单体或单体衍生物。最近鉴定出一种名为GaaR的D-半乳糖醛酸特异性转录因子,并证明它是灰葡萄孢和黑曲霉中参与半乳糖醛酸利用的基因表达的激活剂。通过正向遗传筛选,我们分离出了组成型表达GaaR控制基因的黑曲霉突变体。由于推测gaaR基因中的突变会导致组成型激活的转录因子,因此对11个组成型突变体中的gaaR基因进行了测序,但未发现gaaR中有突变。对五个组成型突变体的全基因组测序揭示了一个特定基因中的等位基因突变,该基因编码一种以前未表征的蛋白质(NRRL3_08194)。NRRL3_08194编码的蛋白质与先前在粗糙脉孢菌(qa-1S)和构巢曲霉(QutR)中鉴定的奎尼酸利用途径的阻遏物具有同源性。结合RNA-seq分析对NRRL3_08194进行缺失表明,NRRL3_08194缺失突变体组成型表达参与半乳糖醛酸利用的基因。有趣的是,NRRL3_08194在基因组中位于gaaR(NRRL3_08195)旁边。与奎尼酸阻遏物的同源性、染色体聚类以及分离突变体的组成型表型表明,NRRL3_08194可能编码一种阻遏物,我们将其命名为GaaX。GaaR-GaaX模块及其染色体组织在子囊菌丝状真菌中是保守的,在氨基酸序列和染色体组织上类似于奎尼酸利用激活剂-阻遏物模块。