Regulation of the Gα-cAMP/PKA signaling pathway in cellulose utilization of Chaetomium globosum

Abstract

BackgroundThe canonical heterotrimeric G protein-cAMP/PKA pathway regulates numerous cellular processes in filamentous fungi. Chaetomium globosum, a saprophytic fungus, is known for producing many secondary metabolites, including cytotoxic chaetoglobosin A (ChA), as well as abundant cellulase and xylanase.ResultsHere we report on the functional characterization of this signaling pathway in C. globosum. We blocked the pathway by knocking down the putative Gα-encoding gene gna1 (in the pG14 mutant). This led to impaired cellulase production and significantly decreased transcription of the major cellulase and xylanase genes. Almost all the glycohydrolase family genes involved in cellulose degradation were downregulated, including the major cellulase genes, cel7a, cel6a, egl1, and egl2. Importantly, the expression of transcription factors was also found to be regulated by gna1, especially Ace1, Clr1/2 and Hap2/3/5 complex. Additionally, carbon metabolic processes including the starch and sucrose metabolism pathway were substantially diminished, as evidenced by RNA-Seq profiling and quantitative reverse transcription (qRT)-PCR. Interestingly, these defects could be restored by simultaneous knockdown of the pkaR gene encoding the regulatory subunit of cAMP-dependent PKA (in the pGP6 mutant) or supplement of the cAMP analog, 8-Br-cAMP. Moreover, the Gα-cAMP/PKA pathway regulating cellulase production is modulated by environmental signals including carbon sources and light, in which VelB/VeA/LaeA complex and ENVOY probably work as downstream effectors.ConclusionThese results revealed, for the first time, the positive role of the heterotrimeric Gα-cAMP/PKA pathway in the regulation of cellulase and xylanase utilization in C. globosum.Electronic supplementary materialThe online version of this article (10.1186/s12934-018-1008-6) contains supplementary material, which is available to authorized users.

Regulating Strategies for Producing Carbohydrate Active Enzymes by Filamentous Fungal Cell Factories

“…The PKA pathway, which plays an antagonistic role in the regulation of CAZymes compared with AMPK pathway, is also involved in the CCR. G protein-coupled receptors, the cellular second messenger cAMP, and adenylate cyclase are all involved in the PKA pathway and affected the downstream targets by phosphorylation cascades (Nogueira et al, 2015;Yang et al, 2018). PKA is essential for CCR as its deletion leads to a misfunction of CCR with impaired nucleus location effect of repressors and partial derepression of CAZymes, which is consistent with the result obtained by the PkaA deletion strain with a varied degree of derepression of cellulase genes under different culture conditions (Kunitake et al, 2019).…”

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“…Additionally, CreA is differentially phosphorylated depending on the presence of PkaA, resulting in altered characteristics for import in the nucleus [25]. A positive role of the cAMP pathway as well as the heterotrimeric G-protein pathway on cellulase gene expression and secondary metabolism was further shown in Chaetomium globosum [26, 27]. Besides functions in development, a role of the cAMP pathway in secondary metabolism was shown for Aspergillus fumigatus , Pestalotiopsis microspora and Fusarium graminearum [28–30].…”

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