The G-protein Coupled Receptor GPR8 Regulates Secondary Metabolism in Trichoderma reesei

Hinterdobler, Wolfgang; Beier, Sabrina; Monroy, Alberto Alonso; Berger, Harald; Dattenböck, Christoph; Schmoll, Monika

doi:10.3389/fbioe.2020.558996

Cited by 13 publications

(18 citation statements)

References 69 publications

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“…Three GPCRs (TRIREDRAFT_53238, TRIREDRAFT_58767, and TRIREDRAFT_62462) might be involved in RSR1 signaling because they showed signi cantly increased transcriptional levels in the rsr1 deletion strain (Table 4). A previous study reported that the TRIREDRAFT_53238 regulates secondary metabolism in T. reesei [50], indicating its regulatory role. Then, we used Δrsr1 as the starting strain to knockout tre62462, tre58767, and tre53238.…”

Section: Discussionmentioning

confidence: 96%

The Ras small GTPase RSR1 regulates cellulase production in Trichoderma reesei

Qiu

Cai

et al. 2023

Preprint

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Background: Lignocellulose is known to be the most abundant renewable resource in the world and has attracted widespread attention because of its ability to produce sugars from the hydrolysis of cellulases and hemicellulases secreted by filamentous fungi. Several studies have revealed that the Ras small GTPase superfamily regulate important cellular physiological processes, including synthesis of metabolites, sporulation, cell growth, cell differentiation, and apoptosis. However, how and to what extent Ras small GTPases are participated in cellulase production remain unknown. Results: In this study, we found that the putative Ras small GTPase RSR1 repressed the expression of cellulases and xylanases. Knockout of rsr1 (∆rsr1) significantly increased cellulase production and decreased the expression levels of ACY1-cAMP-protein kinase A (PKA) signaling pathway genes and intracellular cyclic adenosine monophosphate (cAMP) levels. Loss of acy1 based on ∆rsr1 (∆rsr1∆acy1) could further increase the cellulase production and expression levels of cellulase genes, while overexpression of acy1 based on ∆rsr1 (∆rsr1-OEacy1) significantly reduced the cellulase production and transcriptional levels of cellulase genes. Our results revealed that RSR1 repressed cellulase production via ACY1-cAMP-PKA pathway. Transcriptome analysis revealed significantly increased expression of three G-protein coupled receptors (GPCRs;tre62462, tre58767, tre53238) on rsr1 knockout and approximately two-fold higher expression of ACE3 and XYR1, which transcriptionally activated cellulases. ∆rsr1∆ tre62462 exhibited a decrease in enzyme activity compared to ∆rsr1, while ∆rsr1∆tre58767 and ∆rsr1∆tre53238 showed a remarkable improvement compared to ∆rsr1. We revealed that GPCRs on the membrane sense extracellular signals and transmit them to rsr1 and then to ACY1-cAMP-PKA, thereby repressing the expression of the cellulase activators ACE3 and XYR1. These data indicated the crucial role of Ras small GTPase in regulating cellulase gene expression. Conclusions: Here, we demonstrate that some G-protein-coupled receptors and Ras small GTPases play a key role in signal transduction and cellulase gene regulation in T. reesei. Understanding the roles of these components in the regulation of cellulase gene transcription and understanding the signaling processes in T. reesei can lay the groundwork for understanding and transforming other filamentous fungi.

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Section: Discussionmentioning

confidence: 96%

The Ras small GTPase RSR1 regulates cellulase production in Trichoderma reesei

Qiu

Cai

et al. 2023

Preprint

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“…2 ). 74 Further experiments by Hinterdobler et al 75 revealed another layer of complexity of the tight control of T. reesei on secondary metabolism. Another gene in the vicinity of the sor cluster ( gpr 8), which encodes a class VII G-protein coupled receptor, was shown to have a considerable influence on the regulation of secondary metabolism in T. reesei in darkness.…”

Section: Challenges In Trichoderma Speciesmentioning

confidence: 99%

“…This light dependent regulation of secondary metabolism by GPR8 was found to be mediated in part by the TF YPR2 and the function of the FAD/FMN containing dehydrogenase gene (TrsorD). 75 Another challenge with linking Trichoderma secondary metabolites to their biosynthetic gene clusters is the intertwined and coordinated expression of different gene clusters. For example the disruption of T. hypoxylon tri5 gene which encodes the rst step in trichothecene biosynthesis, disrupted trichothecene biosynthesis as expected, but also resulted in the suppression of another biosynthetic pathway responsible for the production of tricinoloniol acids A-C 27-29 (Scheme 1).…”

Section: Challenges In Trichoderma Speciesmentioning

confidence: 99%

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Molecular methods unravel the biosynthetic potential of Trichoderma species

Shenouda

Cox

2021

RSC Adv.

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“…Ascospore derived progeny were analyzed for the presence of gene deletion and mating type by PCR (Table S1). The functionality of the ham5 gene was con rmed by high resolution melt curve (HRM) analysis, performed as described previously 114 .…”

Section: Construction Of Recombinant Strainsmentioning

confidence: 99%

MAPkinases regulate secondary metabolism, sexual development and light dependent cellulase regulation in Trichoderma reesei

Schalamun

Beier

Hinterdobler

et al. 2022

Preprint

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The filamentous fungus Trichoderma reesei is a prolific producer of plant cell wall degrading enzymes, which are regulated in response to diverse environmental signals for optimal adaptation, but also produces a wide array of secondary metabolites. Available carbon source and light are the strongest cues currently known to impact secreted enzyme levels and an interplay with regulation of secondary metabolism became increasingly obvious in recent years. While cellulase regulation is already known to be modulated by different mitogen activated protein kinase (MAPK) pathways, the relevance of the light signal, which is transmitted by this pathway in other fungi as well, is still unknown in T. reesei as are interconnections to secondary metabolism and chemical communication under mating conditions. Here we show that MAPkinases differentially influence cellulase regulation in light and darkness and that the Hog1 homologue TMK3, but not TMK1 or TMK2 are required for the chemotropic response to glucose in T. reesei. Additionally, MAPkinases regulate production of specific secondary metabolites including trichodimerol and bisorbibutenolid, a bioactive compound with cytostatic effect on cancer cells and deterrent effect on larvae, under conditions facilitating mating, which reflects a defect in chemical communication. Strains lacking either of the MAPkinases become female sterile, indicating the conservation of the role of MAPkinases in sexual fertility also in T. reesei. In summary, our findings substantiate the previously detected interconnection of cellulase regulation with regulation of secondary metabolism as well as the involvement of MAPkinases in light dependent gene regulation of cellulase and secondary metabolite genes in fungi.

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The G-protein Coupled Receptor GPR8 Regulates Secondary Metabolism in Trichoderma reesei

Cited by 13 publications

References 69 publications

The Ras small GTPase RSR1 regulates cellulase production in Trichoderma reesei

The Ras small GTPase RSR1 regulates cellulase production in Trichoderma reesei

Molecular methods unravel the biosynthetic potential of Trichoderma species

MAPkinases regulate secondary metabolism, sexual development and light dependent cellulase regulation in Trichoderma reesei

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