Carbon Catabolite Repression Governs Diverse Physiological Processes and Development in Aspergillus nidulans

Chen, Yingying; Dong, Liguo; Alam, Md Ashiqul; Pardeshi, Lakhansing; Miao, Zhengqiang; Wang, Fang; Tan, Kaeling; Hynes, Michael J.; Kelly, Joseph F.; Wong, Koon Ho

doi:10.1128/mbio.03734-21

Cited by 15 publications

(7 citation statements)

References 111 publications

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“…SCSIO SX7S7, respectively. The successful mutagenesis of the two genes is easy to monitor, as the inactivity of these two genes usually results in a phenotype change with strong growth defects [ 32 , 33 , 34 , 35 ]. For the Spiromastix sp.…”

Section: Resultsmentioning

confidence: 99%

Development of the CRISPR-Cas9 System for the Marine-Derived Fungi Spiromastix sp. SCSIO F190 and Aspergillus sp. SCSIO SX7S7

Chen

Cai

Yang

et al. 2022

JoF

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Marine-derived fungi are emerging as attractive producers of structurally novel secondary metabolites with diverse bioactivities. However, the lack of efficient genetic tools limits the discovery of novel compounds and the elucidation of biosynthesis mechanisms. Here, we firstly established an effective PEG-mediated chemical transformation system for protoplasts in two marine-derived fungi, Spiromastix sp. SCSIO F190 and Aspergillus sp. SCSIO SX7S7. Next, we developed a simple and versatile CRISPR-Cas9-based gene disruption strategy by transforming a target fungus with a single plasmid. We found that the transformation with a circular plasmid encoding cas9, a single-guide RNA (sgRNA), and a selectable marker resulted in a high frequency of targeted and insertional gene mutations in both marine-derived fungal strains. In addition, the histone deacetylase gene rpd3 was mutated using the established CRISPR-Cas9 system, thereby activating novel secondary metabolites that were not produced in the wild-type strain. Taken together, a versatile CRISPR-Cas9-based gene disruption method was established, which will promote the discovery of novel natural products and further biological studies.

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Section: Resultsmentioning

confidence: 99%

Development of the CRISPR-Cas9 System for the Marine-Derived Fungi Spiromastix sp. SCSIO F190 and Aspergillus sp. SCSIO SX7S7

Chen

Cai

Yang

et al. 2022

JoF

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“…Strikingly, CreA suppresses asexual development specifically under glucose but not under maltose, xylose, or ethanol as the sole carbon source. Previous study showed that the unfolded protein response of the Δ creA mutant in A. nidulans is also specific to glucose (Chen et al, 2021). Accordingly, some functions of CreA in addition to CCR depend on carbon sources.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, studies of Magnaporthe oryzae (Hong et al, 2021) and Aspergillus flavus (Fasoyin et al, 2018) have suggested that CreA contributes to hyphal growth, asexual development, and pathogenicity. Recently, the functions of CreA have been investigated in A. nidulans by RNA‐seq and ChIP‐seq approaches, revealing direct roles in various pathways, including secondary metabolism, iron homeostasis, oxidative stress, unfolded protein response (UPR), and asexual and sexual developmental processes, in addition to carbon metabolism (Chen et al, 2021). Interestingly, the UPR of a Δ creA mutant was only observed when grown on glucose but not when acetate or proline was used as the sole carbon source (Chen et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the functions of CreA have been investigated in A. nidulans by RNA‐seq and ChIP‐seq approaches, revealing direct roles in various pathways, including secondary metabolism, iron homeostasis, oxidative stress, unfolded protein response (UPR), and asexual and sexual developmental processes, in addition to carbon metabolism (Chen et al, 2021). Interestingly, the UPR of a Δ creA mutant was only observed when grown on glucose but not when acetate or proline was used as the sole carbon source (Chen et al, 2021). These results suggest that some functions of CreA depend on the carbon source.…”

Section: Introductionmentioning

confidence: 99%

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Transcription factor CreA is involved in the inverse regulation of biofilm formation and asexual development through distinct pathways in Aspergillus fumigatus

Liu,

Lu,

Dai

et al. 2023

Molecular Microbiology

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The exopolysaccharide galactosaminogalactan (GAG) contributes to biofilm formation and virulence in the pathogenic fungus Aspergillus fumigatus. Increasing evidence indicates that GAG production is inversely linked with asexual development. However, the mechanisms underlying this regulatory relationship are unclear. In this study, we found that the dysfunction of CreA, a conserved transcription factor involved in carbon catabolite repression in many fungal species, causes abnormal asexual development (conidiation) under liquid‐submerged culture conditions specifically in the presence of glucose. The loss of creA decreased GAG production independent of carbon sources. Furthermore, CreA contributed to asexual development and GAG production via distinct pathways. CreA promoted A. fumigatus GAG production by positively regulating GAG biosynthetic genes (uge3 and agd3). CreA suppressed asexual development in glucose liquid‐submerged culture conditions via central conidiation genes (brlA, abaA, and wetA) and their upstream activators (flbC and flbD). Restoration of brlA expression to the wild‐type level by flbC or flbD deletion abolished the abnormal submerged conidiation in the creA null mutant but did not restore GAG production. The C‐terminal region of CreA was crucial for the suppression of asexual development, and the repressive domain contributed to GAG production. Overall, CreA is involved in GAG production and asexual development in an inverse manner.

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“…In T. reesei , CreA was considered as a regulator of the glucose assimilation rate 51 . Recent research has also shown that CreA could bind not only to the promoter of cellulose related genes, but also to the promoter of other genes to play a primary role in diverse physiological processes, such as carbon metabolism, secondary metabolism, iron homeostasis, oxidative stress response, development, N-glycan production, unfolded protein response, and nutrient and ion transport in A. nidulans 52 . Beyond carbon metabolism regulation, studies in various fungal species indicate additional CreA functions.…”

Section: Discussionmentioning

confidence: 99%

The CBS/H2S signalling pathway regulated by the carbon repressor CreA promotes cellulose utilization in Ganoderma lucidum

Shangguan,

Qiao,

Liu

et al. 2024

Commun Biol

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Cellulose is an important abundant renewable resource on Earth, and the microbial cellulose utilization mechanism has attracted extensive attention. Recently, some signalling molecules have been found to regulate cellulose utilization and the discovery of underlying signals has recently attracted extensive attention. In this paper, we found that the hydrogen sulfide (H2S) concentration under cellulose culture condition increased to approximately 2.3-fold compared with that under glucose culture condition in Ganoderma lucidum. Further evidence shown that cellulase activities of G. lucidum were improved by 18.2-27.6% through increasing H2S concentration. Then, we observed that the carbon repressor CreA inhibited H2S biosynthesis in G. lucidum by binding to the promoter of cbs, a key gene for H2S biosynthesis, at “CTGGGG”. In our study, we reported for the first time that H2S increased the cellulose utilization in G. lucidum, and analyzed the mechanism of H2S biosynthesis induced by cellulose. This study not only enriches the understanding of the microbial cellulose utilization mechanism but also provides a reference for the analysis of the physiological function of H2S signals.

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Carbon Catabolite Repression Governs Diverse Physiological Processes and Development in Aspergillus nidulans

Cited by 15 publications

References 111 publications

Development of the CRISPR-Cas9 System for the Marine-Derived Fungi Spiromastix sp. SCSIO F190 and Aspergillus sp. SCSIO SX7S7

Development of the CRISPR-Cas9 System for the Marine-Derived Fungi Spiromastix sp. SCSIO F190 and Aspergillus sp. SCSIO SX7S7

Transcription factor CreA is involved in the inverse regulation of biofilm formation and asexual development through distinct pathways in Aspergillus fumigatus

The CBS/H2S signalling pathway regulated by the carbon repressor CreA promotes cellulose utilization in Ganoderma lucidum

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