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Prof. Shihua Wang
Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, Key Laboratory of Biopesticide and Chemical Biology of Education Ministry, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China

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0 Controlling
0 Detection
0 Mycotoxins
0 Antibody
0 Aspergillus

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Review
Published: 17 August 2021 in Journal of Fungi
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Aspergillus flavus (A. flavus) is a ubiquitous and opportunistic fungal pathogen that causes invasive and non-invasive aspergillosis in humans and animals. This fungus is also capable of infecting a large number of agriculture crops (e.g., peanuts, maze, cotton seeds, rice, etc.), causing economic losses and posing serious food-safety concerns when these crops are contaminated with aflatoxins, the most potent naturally occurring carcinogens. In particular, A. flavus and aflatoxins are intensely studied, and they continue to receive considerable attention due to their detrimental effects on humans, animals, and crops. Although several studies have been published focusing on the biosynthesis of the aforementioned secondary metabolites, some of the molecular mechanisms (e.g., posttranslational modifications, transcription factors, transcriptome, proteomics, metabolomics and transcriptome, etc.) involved in the fungal development and aflatoxin biosynthesis in A. flavus are still not fully understood. In this study, a review of the recently published studies on the function of the genes and the molecular mechanisms involved in development of A. flavus and the production of its secondary metabolites is presented. It is hoped that the information provided in this review will help readers to develop effective strategies to reduce A. flavus infection and aflatoxin production.

ACS Style

Elisabeth Tumukunde; Rui Xie; Shihua Wang. Updates on the Functions and Molecular Mechanisms of the Genes Involved in Aspergillus flavus Development and Biosynthesis of Aflatoxins. Journal of Fungi 2021, 7, 666 .

AMA Style

Elisabeth Tumukunde, Rui Xie, Shihua Wang. Updates on the Functions and Molecular Mechanisms of the Genes Involved in Aspergillus flavus Development and Biosynthesis of Aflatoxins. Journal of Fungi. 2021; 7 (8):666.

Chicago/Turabian Style

Elisabeth Tumukunde; Rui Xie; Shihua Wang. 2021. "Updates on the Functions and Molecular Mechanisms of the Genes Involved in Aspergillus flavus Development and Biosynthesis of Aflatoxins." Journal of Fungi 7, no. 8: 666.

Research article
Published: 07 June 2021 in Environmental Microbiology
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Ras subfamily proteins are molecular switches in signal transduction pathways of many eukaryotes that regulate a variety of cellular processes. Here, the Ras subfamily, encoded by six genes, was identified in Aspergillus flavus: rasA, rasB, rasC, rab-33, rheb and rsr1. The rsr1 deletion mutant (∆rsr1), rheb deletion mutant (∆rheb) and double deletion mutant (∆rheb/rsr1) displayed significantly decreased growth and sporulation. Sclerotia formation was significantly decreased for ∆rheb or ∆rheb/rsr1 but increased for ∆rsr1. Aflatoxin production was significantly increased in ∆rheb but decreased in ∆rsr1 and ∆rheb/rsr1. We found that rsr1 and rheb are crucial for the pathogenicity of A. flavus. Quantitative proteomics identified 520 differentially expressed proteins (DEPs) for the ∆rsr1 mutant and 133 DEPs for the ∆rheb mutant. These DEPs were annotated in multiple biological processes and KEGG pathways in A. flavus. Importantly, we identified the cytokinesis protein SepA in the protein–protein interaction network of rsr1, and deletion mutants showed that SepA has pleiotropic effects on growth and AF biosynthesis, which may depend on Rsr1 for regulation in A. flavus. Our results indicated that these Ras subfamily proteins exhibited functional redundancy with each other but there were also differences in A. flavus.

ACS Style

Zhuo Zhu; Gengli Ma; Mingkun Yang; Can Tan; Guang Yang; Sen Wang; Na Li; Feng Ge; Shihua Wang. Ras Subfamily GTPases Regulate Development, Aflatoxin Biosynthesis and Pathogenicity in the Fungus Aspergillus flavus. Environmental Microbiology 2021, 1 .

AMA Style

Zhuo Zhu, Gengli Ma, Mingkun Yang, Can Tan, Guang Yang, Sen Wang, Na Li, Feng Ge, Shihua Wang. Ras Subfamily GTPases Regulate Development, Aflatoxin Biosynthesis and Pathogenicity in the Fungus Aspergillus flavus. Environmental Microbiology. 2021; ():1.

Chicago/Turabian Style

Zhuo Zhu; Gengli Ma; Mingkun Yang; Can Tan; Guang Yang; Sen Wang; Na Li; Feng Ge; Shihua Wang. 2021. "Ras Subfamily GTPases Regulate Development, Aflatoxin Biosynthesis and Pathogenicity in the Fungus Aspergillus flavus." Environmental Microbiology , no. : 1.

Journal article
Published: 07 April 2021 in IMA Fungus
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Aspergillus flavusis a common saprophytic filamentous fungus that produces the highly toxic natural compound aflatoxin during its growth process. Synthesis of the aflatoxins, which can contaminate food crops causing huge losses to the agricultural economy, is often regulated by epigenetic modification, such as the histone acetyltransferase. In this study, we usedAspergillus flavusas an experimental model to construct the acetyltransferase genertt109knockout strain (△rtt109) and its complementary strain (△rtt109·com) by homologous recombination. The growth of △rtt109was significantly suppressed compared to the wild type (WT) strain and the △rtt109·com strain. The sclerotium of △rtt109grew smaller, and the amount of sclerotia generated by △rtt109was significantly reduced. The number of conidiums of △rtt109was significantly reduced, especially on the yeast extract sucrose (YES) solid medium. The amount of aflatoxins synthesized by △rtt109in the PDB liquid medium was significantly decreased We also found that the △rtt109strain was extremely sensitive to DNA damage stress. Through the maize seed infection experiment, we found that the growth of △rtt109on the surface of affected corn was largely reduced, and the amount of aerial mycelium decreased significantly, which was consistent with the results on the artificial medium. We further found that H3K9 was the acetylated target of Rtt109 inA. flavus. In conclusion, Rtt109 participated in the growth, conidium formation, sclerotia generation, aflatoxin synthesis, environmental stress response, regulation of infection ofA. flavus.The results from this study ofrtt109showed data for acetylation in the regulation of life processes and provided a new thought regarding the prevention and control ofA. flavushazards.

ACS Style

Ruilin Sun; Meifang Wen; Lianghuan Wu; Huahui Lan; Jun Yuan; Shihua Wang. The Fungi-specific histone Acetyltransferase Rtt109 mediates morphogenesis, Aflatoxin synthesis and pathogenicity in Aspergillus flavus by acetylating H3K9. IMA Fungus 2021, 12, 1 -14.

AMA Style

Ruilin Sun, Meifang Wen, Lianghuan Wu, Huahui Lan, Jun Yuan, Shihua Wang. The Fungi-specific histone Acetyltransferase Rtt109 mediates morphogenesis, Aflatoxin synthesis and pathogenicity in Aspergillus flavus by acetylating H3K9. IMA Fungus. 2021; 12 (1):1-14.

Chicago/Turabian Style

Ruilin Sun; Meifang Wen; Lianghuan Wu; Huahui Lan; Jun Yuan; Shihua Wang. 2021. "The Fungi-specific histone Acetyltransferase Rtt109 mediates morphogenesis, Aflatoxin synthesis and pathogenicity in Aspergillus flavus by acetylating H3K9." IMA Fungus 12, no. 1: 1-14.

Journal article
Published: 01 January 2021 in Molecular & Cellular Proteomics
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Aspergillus flavus (A. flavus), a pathogenic fungus, can produce carcinogenic and toxic aflatoxins that are a serious agricultural and medical threat worldwide. Attempts to decipher the aflatoxin biosynthetic pathway have been hampered by the lack of a high-quality genome annotation for A. flavus. To address this gap, we performed a comprehensive proteogenomic analysis using high-accuracy mass spectrometry data for this pathogen. The resulting high-quality data set confirmed the translation of 8724 previously predicted genes and identified 732 novel proteins, 269 splice variants, 447 single amino acid variants, 188 revised genes. A subset of novel proteins was experimentally validated by RT-PCR and synthetic peptides. Further functional annotation suggested that a number of the identified novel proteins may play roles in aflatoxin biosynthesis and stress responses in A. flavus. This comprehensive strategy also identified a wide range of posttranslational modifications (PTMs), including 3461 modification sites from 1765 proteins. Functional analysis suggested the involvement of these modified proteins in the regulation of cellular metabolic and aflatoxin biosynthetic pathways. Together, we provided a high-quality annotation of A. flavus genome and revealed novel insights into the mechanisms of aflatoxin production and pathogenicity in this pathogen.

ACS Style

Mingkun Yang; Zhuo Zhu; Zhenhong Zhuang; Youhuang Bai; Shihua Wang; Feng Ge. Proteogenomic Characterization of the Pathogenic Fungus Aspergillus flavus Reveals Novel Genes Involved in Aflatoxin Production. Molecular & Cellular Proteomics 2021, 20, 100013 .

AMA Style

Mingkun Yang, Zhuo Zhu, Zhenhong Zhuang, Youhuang Bai, Shihua Wang, Feng Ge. Proteogenomic Characterization of the Pathogenic Fungus Aspergillus flavus Reveals Novel Genes Involved in Aflatoxin Production. Molecular & Cellular Proteomics. 2021; 20 ():100013.

Chicago/Turabian Style

Mingkun Yang; Zhuo Zhu; Zhenhong Zhuang; Youhuang Bai; Shihua Wang; Feng Ge. 2021. "Proteogenomic Characterization of the Pathogenic Fungus Aspergillus flavus Reveals Novel Genes Involved in Aflatoxin Production." Molecular & Cellular Proteomics 20, no. : 100013.

Journal article
Published: 31 December 2020 in Journal of Hazardous Materials
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Owing to the threat of cadmium (Cd2+) to public health, it is an urgent demand to develop effective, sensitive, and rapid methods for the detection of cadmium. In this study, indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and immunochromatographic test strips (ICTS) were established for the determination of Cd2+ based on the obtained mAb with high specificity and high affinity (Kaff = 3.0 × 109 L/moL). The linear range of ic-ELISA detection was 0.03–1.11 ng/mL and 50% inhibitive concentration (IC50) of cadmium ion was determined to be 0.15 ng/mL. The visual limit of detection (vLOD) of the AuNS-based strip was 0.375 ng/mL. The vLOD of AuNF-based strip using higher intensity reporter determined to be 0.03 ng/mL, which was enhanced 12 times compared to the traditional strip. In summary, the developed immunoassays based on mAb shows great potential for monitoring the cadmium ion in environmental samples.

ACS Style

Sumei Ling; Qiang Zhao; Muhammad Naeem Iqbal; Mingke Dong; Xiulan Li; Ming Lin; Rongzhi Wang; Feiya Lei; Caizhen He; Shihua Wang. Development of immunoassay methods based on monoclonal antibody and its application in the determination of cadmium ion. Journal of Hazardous Materials 2020, 411, 124992 .

AMA Style

Sumei Ling, Qiang Zhao, Muhammad Naeem Iqbal, Mingke Dong, Xiulan Li, Ming Lin, Rongzhi Wang, Feiya Lei, Caizhen He, Shihua Wang. Development of immunoassay methods based on monoclonal antibody and its application in the determination of cadmium ion. Journal of Hazardous Materials. 2020; 411 ():124992.

Chicago/Turabian Style

Sumei Ling; Qiang Zhao; Muhammad Naeem Iqbal; Mingke Dong; Xiulan Li; Ming Lin; Rongzhi Wang; Feiya Lei; Caizhen He; Shihua Wang. 2020. "Development of immunoassay methods based on monoclonal antibody and its application in the determination of cadmium ion." Journal of Hazardous Materials 411, no. : 124992.

Journal article
Published: 13 November 2020 in Toxins
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The RNA polymerase II (Pol II) transcription process is coordinated by the reversible phosphorylation of its largest subunit-carboxy terminal domain (CTD). Ssu72 is identified as a CTD phosphatase with specificity for phosphorylation of Ser5 and Ser7 and plays critical roles in regulation of transcription cycle in eukaryotes. However, the biofunction of Ssu72 is still unknown in Aspergillus flavus, which is a plant pathogenic fungus and produces one of the most toxic mycotoxins-aflatoxin. Here, we identified a putative phosphatase Ssu72 and investigated the function of Ssu72 in A. flavus. Deletion of ssu72 resulted in severe defects in vegetative growth, conidiation and sclerotia formation. Additionally, we found that phosphatase Ssu72 positively regulates aflatoxin production through regulating expression of aflatoxin biosynthesis cluster genes. Notably, seeds infection assays indicated that phosphatase Ssu72 is crucial for pathogenicity of A. flavus. Furthermore, the Δssu72 mutant exhibited more sensitivity to osmotic and oxidative stresses. Taken together, our study suggests that the putative phosphatase Ssu72 is involved in fungal development, aflatoxin production and pathogenicity in A. flavus, and may provide a novel strategy to prevent the contamination of this pathogenic fungus.

ACS Style

Guang Yang; Xiaohong Cao; Ling Qin; Lijuan Yan; Rongsheng Hong; Jun Yuan; Shihua Wang. Ssu72 Regulates Fungal Development, Aflatoxin Biosynthesis and Pathogenicity in Aspergillus flavus. Toxins 2020, 12, 717 .

AMA Style

Guang Yang, Xiaohong Cao, Ling Qin, Lijuan Yan, Rongsheng Hong, Jun Yuan, Shihua Wang. Ssu72 Regulates Fungal Development, Aflatoxin Biosynthesis and Pathogenicity in Aspergillus flavus. Toxins. 2020; 12 (11):717.

Chicago/Turabian Style

Guang Yang; Xiaohong Cao; Ling Qin; Lijuan Yan; Rongsheng Hong; Jun Yuan; Shihua Wang. 2020. "Ssu72 Regulates Fungal Development, Aflatoxin Biosynthesis and Pathogenicity in Aspergillus flavus." Toxins 12, no. 11: 717.

Research article
Published: 07 November 2020 in Microbial Biotechnology
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As a pathogenic fungus, Aspergillus flavus can produce carcinogenic aflatoxins (AFs), which poses a great threat to crops and animals. Msb2, the signalling mucin protein, is a part of mitogen‐activated protein kinase (MAPK) pathway which contributes to a range of physiological processes. In this study, the roles of membrane mucin Msb2 were explored in A. flavus by the application of gene disruption. The deletion of msb2 gene (Δmsb2) caused defects in vegetative growth, sporulation and sclerotia formation when compared to WT and complement strain (Δmsb2C) in A. flavus. Using thin‐layer chromatography (TLC) and high‐performance liquid chromatography (HPLC) analysis, it was found that deletion of msb2 down‐regulated aflatoxin B1 (AFB1) synthesis and decreased the infection capacity of A. flavus. Consistently, Msb2 responds to cell wall stress and osmotic stress by positively regulating the phosphorylation of MAP kinase. Notably, Δmsb2 mutant exhibited cell wall defect, and it was more sensitive to inhibitor caspofungin when compared to WT and Δmsb2C. Taking together, these results revealed that Msb2 plays key roles in morphological development process, stresses adaptation, secondary metabolism and pathogenicity in fungus A. flavus.

ACS Style

Ling Qin; Ding Li; Jiaru Zhao; Guang Yang; Yinchun Wang; Kunlong Yang; Elisabeth Tumukunde; Shihua Wang; Jun Yuan. The membrane mucin Msb2 regulates aflatoxin biosynthesis and pathogenicity in fungus Aspergillus flavus. Microbial Biotechnology 2020, 14, 628 -642.

AMA Style

Ling Qin, Ding Li, Jiaru Zhao, Guang Yang, Yinchun Wang, Kunlong Yang, Elisabeth Tumukunde, Shihua Wang, Jun Yuan. The membrane mucin Msb2 regulates aflatoxin biosynthesis and pathogenicity in fungus Aspergillus flavus. Microbial Biotechnology. 2020; 14 (2):628-642.

Chicago/Turabian Style

Ling Qin; Ding Li; Jiaru Zhao; Guang Yang; Yinchun Wang; Kunlong Yang; Elisabeth Tumukunde; Shihua Wang; Jun Yuan. 2020. "The membrane mucin Msb2 regulates aflatoxin biosynthesis and pathogenicity in fungus Aspergillus flavus." Microbial Biotechnology 14, no. 2: 628-642.

Journal article
Published: 23 September 2020 in International Journal of Molecular Sciences
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Aflatoxins (AFs) have always been regarded as the most effective carcinogens, posing a great threat to agriculture, food safety, and human health. Aspergillus flavus is the major producer of aflatoxin contamination in crops. The prevention and control of A. flavus and aflatoxin continues to be a global problem. In this study, we demonstrated that the cell-free culture filtrate of Aspergillus oryzae and a non-aflatoxigenic A. flavus can effectively inhibit the production of AFB1 and the growth and reproduction of A. flavus, indicating that both of the non-aflatoxigenic Aspergillus strains secrete inhibitory compounds. Further transcriptome sequencing was performed to analyze the inhibitory mechanism of A. flavus treated with fermenting cultures, and the results revealed that genes involved in the AF biosynthesis pathway and other biosynthetic gene clusters were significantly downregulated, which might be caused by the reduced expression of specific regulators, such as AflS, FarB, and MtfA. The WGCNA results further revealed that genes involved in the TCA cycle and glycolysis were potentially involved in aflatoxin biosynthesis. Our comparative transcriptomics also revealed that two conidia transcriptional factors, brlA and abaA, were found to be significantly downregulated, which might lead to the downregulation of conidiation-specific genes, such as the conidial hydrophobins genes rodA and rodB. In summary, our research provides new insights for the molecular mechanism of controlling AF synthesis to control the proliferation of A. flavus and AF pollution.

ACS Style

Kunlong Yang; Qingru Geng; Fengqin Song; Xiaona He; Tianran Hu; Shihua Wang; Jun Tian. Transcriptome Sequencing Revealed an Inhibitory Mechanism of Aspergillus flavus Asexual Development and Aflatoxin Metabolism by Soy-Fermenting Non-Aflatoxigenic Aspergillus. International Journal of Molecular Sciences 2020, 21, 6994 .

AMA Style

Kunlong Yang, Qingru Geng, Fengqin Song, Xiaona He, Tianran Hu, Shihua Wang, Jun Tian. Transcriptome Sequencing Revealed an Inhibitory Mechanism of Aspergillus flavus Asexual Development and Aflatoxin Metabolism by Soy-Fermenting Non-Aflatoxigenic Aspergillus. International Journal of Molecular Sciences. 2020; 21 (19):6994.

Chicago/Turabian Style

Kunlong Yang; Qingru Geng; Fengqin Song; Xiaona He; Tianran Hu; Shihua Wang; Jun Tian. 2020. "Transcriptome Sequencing Revealed an Inhibitory Mechanism of Aspergillus flavus Asexual Development and Aflatoxin Metabolism by Soy-Fermenting Non-Aflatoxigenic Aspergillus." International Journal of Molecular Sciences 21, no. 19: 6994.

Journal article
Published: 13 August 2020 in Food Chemistry
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Lactoferrin (LF), a bioactive multifunctional protein of the transferrin family, is found mainly in the secretions of all mammals, especially in milk. In the present study, a hybridoma cell (LF8) secreting IgG against bovine LF was screened, and the purified LF8 mAb showed high specificity and affinity to bovine LF. The linear range of ic-ELISA to detect LF was 9.76∼625 ng/mL, with a limit of detection (LOD) of 0.01 ng/mL. The average recovery of intra- and inter-assay were (104.45±4.12)% and (107.13±4.72)%, respectively. The LOD of colloidal gold- and AuNFs-based strip by naked eye were 9.7 and 2.4 ng/mL, respectively, and the detection time was less than 10 min without any samples pretreatment and expensive equipment. The developed ELISA and lateral flow immunosensors based on specific IgG could be used directly for rapid detection of the bovine LF content in cow milk samples.

ACS Style

Rongzhi Wang; Juncheng Wang; Haimei Liu; Yehong Gao; Qiang Zhao; Sumei Ling; Shihua Wang. Sensitive immunoassays based on specific monoclonal IgG for determination of bovine lactoferrin in cow milk samples. Food Chemistry 2020, 338, 127820 .

AMA Style

Rongzhi Wang, Juncheng Wang, Haimei Liu, Yehong Gao, Qiang Zhao, Sumei Ling, Shihua Wang. Sensitive immunoassays based on specific monoclonal IgG for determination of bovine lactoferrin in cow milk samples. Food Chemistry. 2020; 338 ():127820.

Chicago/Turabian Style

Rongzhi Wang; Juncheng Wang; Haimei Liu; Yehong Gao; Qiang Zhao; Sumei Ling; Shihua Wang. 2020. "Sensitive immunoassays based on specific monoclonal IgG for determination of bovine lactoferrin in cow milk samples." Food Chemistry 338, no. : 127820.

Journal article
Published: 23 April 2020 in Toxins
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Fungal secondary metabolites play important roles not only in fungal ecology but also in humans living as beneficial medicine or harmful toxins. In filamentous fungi, bZIP-type transcription factors (TFs) are associated with the proteins involved in oxidative stress response and secondary metabolism. In this study, a connection between a bZIP TF and oxidative stress induction of secondary metabolism is uncovered in an opportunistic pathogen Aspergillus flavus, which produces carcinogenic and mutagenic aflatoxins. The bZIP transcription factor AflRsmA was identified by a homology research of A. flavus genome with the bZIP protein RsmA, involved in secondary metabolites production in Aspergillus nidulans. The AflrsmA deletion strain (ΔAflrsmA) displayed less sensitivity to the oxidative reagents tert-Butyl hydroperoxide (tBOOH) in comparison with wild type (WT) and AflrsmA overexpression strain (AflrsmAOE), while AflrsmAOE strain increased sensitivity to the oxidative reagents menadione sodium bisulfite (MSB) compared to WT and ΔAflrsmA strains. Without oxidative treatment, aflatoxin B1 (AFB1) production of ΔAflrsmA strains was consistent with that of WT, but AflrsmAOE strain produced more AFB1 than WT; tBOOH and MSB treatment decreased AFB1 production of ΔAflrsmA compared to WT. Besides, relative to WT, ΔAflrsmA strain decreased sclerotia, while AflrsmAOE strain increased sclerotia. The decrease of AFB1 by ΔAflrsmA but increase of AFB1 by AflrsmAOE was on corn. Our results suggest that AFB1 biosynthesis is regulated by AflRsmA by oxidative stress pathways and provide insights into a possible function of AflRsmA in mediating AFB1 biosynthesis response host defense in pathogen A. flavus.

ACS Style

Xinua Wang; Wenjie Zha; Linlin Liang; Opemipo Esther Fasoyin; Lihan Wu; Shihua Wang. The bZIP Transcription Factor AflRsmA Regulates Aflatoxin B1 Biosynthesis, Oxidative Stress Response and Sclerotium Formation in Aspergillus flavus. Toxins 2020, 12, 271 .

AMA Style

Xinua Wang, Wenjie Zha, Linlin Liang, Opemipo Esther Fasoyin, Lihan Wu, Shihua Wang. The bZIP Transcription Factor AflRsmA Regulates Aflatoxin B1 Biosynthesis, Oxidative Stress Response and Sclerotium Formation in Aspergillus flavus. Toxins. 2020; 12 (4):271.

Chicago/Turabian Style

Xinua Wang; Wenjie Zha; Linlin Liang; Opemipo Esther Fasoyin; Lihan Wu; Shihua Wang. 2020. "The bZIP Transcription Factor AflRsmA Regulates Aflatoxin B1 Biosynthesis, Oxidative Stress Response and Sclerotium Formation in Aspergillus flavus." Toxins 12, no. 4: 271.

Research article
Published: 01 April 2020 in Molecular Plant-Microbe Interactions®
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Aspergillus flavus represents an important fungal pathogen, causing severe economic losses in crops. The mitogen-activated protein (MAP) kinase signaling pathway contributes to many physiological processes, but its precise role in A. flavus is not yet fully understood. In this study, we focused on the AflBck1 gene, which encodes a MAP kinase kinase kinase of the Slt2-MAPK pathway. Targeted deletion of AflBck1 led to a significant defect in growth and development, and a AflBck1-deleted mutant (∆AflBck1) showed higher sensitivity to cell-wall stress than wild type (WT). Importantly, we observed that ∆AflBck1 displayed an enhanced ability to produce aflatoxin, a potential carcinogenic mycotoxin. However, the pathogenicity of the ∆AflBck1 mutant was markedly reduced in peanut seeds. We also presented evidence that AflBck1 was genetically epistatic to AflMkk2 in the Slt2-MAPK pathway. Finally, we found that loss of the proline-rich region at the N terminus of AflBck1 affected the reproduction of A. flavus. Collectively, this study not only extended the understanding that the MAPK pathway regulated A. flavus pathogenicity but also provided a possible strategy to control A. flavus contamination.

ACS Style

Feng Zhang; Luhua Huang; Jili Deng; Can Tan; Longpo Geng; Yun Liao; Jun Yuan; Shihua Wang. A Cell Wall Integrity–Related MAP Kinase Kinase Kinase AflBck1 Is Required for Growth and Virulence in Fungus Aspergillus flavus. Molecular Plant-Microbe Interactions® 2020, 33, 680 -692.

AMA Style

Feng Zhang, Luhua Huang, Jili Deng, Can Tan, Longpo Geng, Yun Liao, Jun Yuan, Shihua Wang. A Cell Wall Integrity–Related MAP Kinase Kinase Kinase AflBck1 Is Required for Growth and Virulence in Fungus Aspergillus flavus. Molecular Plant-Microbe Interactions®. 2020; 33 (4):680-692.

Chicago/Turabian Style

Feng Zhang; Luhua Huang; Jili Deng; Can Tan; Longpo Geng; Yun Liao; Jun Yuan; Shihua Wang. 2020. "A Cell Wall Integrity–Related MAP Kinase Kinase Kinase AflBck1 Is Required for Growth and Virulence in Fungus Aspergillus flavus." Molecular Plant-Microbe Interactions® 33, no. 4: 680-692.

Journal article
Published: 02 March 2020 in International Journal of Food Microbiology
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Aflatoxin contamination in food and feed products has been brought into sharp focus over the last few decades in the world. However, there is no effective strategy for solving the problem thus far. Therefore, basic research on the aflatoxin-producer Aspergillus flavus is an urgent need. The vital role of mitogen-activated protein kinases (MAPKs) in signal transduction has been documented in various pathogenic fungi, but their functions in A. flavus have rarely been investigated. Herein, we characterized the detailed function of one of these MAPKs, AflSlt2. Targeted deletion of AflSlt2 gene indicates that this kinase is required for vegetative growth, conidia generation, and sclerotium formation. The analysis of AflSlt2 deletion mutant revealed hypersensitivity to cell wall-damaging chemicals and resistance against hydrogen peroxide. Interestingly, the ability of the ΔAflSlt2 mutant to generate aflatoxins in medium was significantly increased compared to wild type. However, a pathogenicity assay indicated that the ΔAflSlt2 mutant was deficient in peanut infection. Site-directed mutation study uncovered that the function of AflSlt2 was dependent on the phosphorylated residues (Thr-186 and Tyr-188) within the activation loop and the phosphotransfer residue (Lys-52) within the subdomain II. Interestingly, an autophosphorylation mutant of AflSlt2 (AflSlt2R66S) displayed wild type-like phenotypes. Bringing these observations together, we propose that Slt2-MAPK pathway is involved in development, stress response, aflatoxin biosynthesis, and pathogenicity in A. flavus. This study may be useful to unveil the regulation mechanism of aflatoxin biosynthesis and provide strategy to control A. flavus contamination.

ACS Style

Feng Zhang; Longpo Geng; Jili Deng; Luhua Huang; Hong Zhong; Sijie Xin; Opemipo Esther Fasoyin; Shihua Wang. The MAP kinase AflSlt2 modulates aflatoxin biosynthesis and peanut infection in the fungus Aspergillus flavus. International Journal of Food Microbiology 2020, 322, 108576 .

AMA Style

Feng Zhang, Longpo Geng, Jili Deng, Luhua Huang, Hong Zhong, Sijie Xin, Opemipo Esther Fasoyin, Shihua Wang. The MAP kinase AflSlt2 modulates aflatoxin biosynthesis and peanut infection in the fungus Aspergillus flavus. International Journal of Food Microbiology. 2020; 322 ():108576.

Chicago/Turabian Style

Feng Zhang; Longpo Geng; Jili Deng; Luhua Huang; Hong Zhong; Sijie Xin; Opemipo Esther Fasoyin; Shihua Wang. 2020. "The MAP kinase AflSlt2 modulates aflatoxin biosynthesis and peanut infection in the fungus Aspergillus flavus." International Journal of Food Microbiology 322, no. : 108576.

Journal article
Published: 19 January 2020 in Toxins
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Aspergillus flavus is one of the most opportunistic pathogens invading many important oilseed crops and foodstuffs with such toxic secondary metabolites as aflatoxin (AF) and Cyclopiazonic acid. We previously used the DNA methylation inhibitor 5-azacytidine to treat with an AF-producing A. flavus A133 strain, and isolated a mutant (NT) of A. flavus, which displayed impaired abilities of AF biosynthesis and fungal development. In this study, gas chromatography–mass spectrometry (GC-MS) analysis was used to reveal the metabolic changes between these two strains. A total of 1181 volatiles were identified in these two strains, among which 490 volatiles were found in these two strains in vitro and 332 volatiles were found in vivo. The NT mutant was found to produce decreasing volatile compounds, among which most of the fatty acid-derived volatiles were significantly downregulated in the NT mutant compared to the A133 strain, which are important precursors for AF biosynthesis. Two antioxidants and most of the amino acids derived volatiles were found significantly upregulated in the NT mutant. Overall, our results reveal the difference of metabolic profiles in two different A. flavus isolates, which may provide valuable information for controlling infections of this fungal pathogen.

ACS Style

Fengqin Song; Qingru Geng; Xuewei Wang; Xiaoqing Gao; Xiaona He; Wei Zhao; Huahui Lan; Jun Tian; Kunlong Yang; Shihua Wang. Gas Chromatography–Mass Spectrometry Profiling of Volatile Compounds Reveals Metabolic Changes in a Non-Aflatoxigenic Aspergillus flavus Induced by 5-Azacytidine. Toxins 2020, 12, 57 .

AMA Style

Fengqin Song, Qingru Geng, Xuewei Wang, Xiaoqing Gao, Xiaona He, Wei Zhao, Huahui Lan, Jun Tian, Kunlong Yang, Shihua Wang. Gas Chromatography–Mass Spectrometry Profiling of Volatile Compounds Reveals Metabolic Changes in a Non-Aflatoxigenic Aspergillus flavus Induced by 5-Azacytidine. Toxins. 2020; 12 (1):57.

Chicago/Turabian Style

Fengqin Song; Qingru Geng; Xuewei Wang; Xiaoqing Gao; Xiaona He; Wei Zhao; Huahui Lan; Jun Tian; Kunlong Yang; Shihua Wang. 2020. "Gas Chromatography–Mass Spectrometry Profiling of Volatile Compounds Reveals Metabolic Changes in a Non-Aflatoxigenic Aspergillus flavus Induced by 5-Azacytidine." Toxins 12, no. 1: 57.

Journal article
Published: 13 December 2019 in Toxins
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Various signaling pathways in filamentous fungi help cells receive and respond to environmental information. Previous studies have shown that the mitogen-activated protein kinase (MAPK) pathway is phosphorylation-dependent and activated by different kinase proteins. Serine/threonine kinase plays a very important role in the MAPK pathway. In this study, we selected the serine/threonine kinase AflSte20 in Aspergillus flavus for functional study. By constructing Aflste20 knockout mutants and complemented strains, it was proven that the Aflste20 knockout mutant (ΔAflste20) showed a significant decrease in growth, sporogenesis, sclerotinogenesis, virulence, and infection compared to the WT (wild type) and complemented strain (ΔAflste20C). Further research indicated that ΔAflste20 has more sensitivity characteristics than WT and ΔAflste20C under various stimuli such as osmotic stress and other types of environmental stresses. Above all, our study showed that the mitogen-activated kinase AflSte20 plays an important role in the growth, conidia production, stress response and sclerotia formation, as well as aflatoxin biosynthesis, in A. flavus.

ACS Style

Ding Li; Ling Qin; Yinchun Wang; Qingchen Xie; Na Li; Shihua Wang; Jun Yuan. AflSte20 Regulates Morphogenesis, Stress Response, and Aflatoxin Biosynthesis of Aspergillus flavus. Toxins 2019, 11, 730 .

AMA Style

Ding Li, Ling Qin, Yinchun Wang, Qingchen Xie, Na Li, Shihua Wang, Jun Yuan. AflSte20 Regulates Morphogenesis, Stress Response, and Aflatoxin Biosynthesis of Aspergillus flavus. Toxins. 2019; 11 (12):730.

Chicago/Turabian Style

Ding Li; Ling Qin; Yinchun Wang; Qingchen Xie; Na Li; Shihua Wang; Jun Yuan. 2019. "AflSte20 Regulates Morphogenesis, Stress Response, and Aflatoxin Biosynthesis of Aspergillus flavus." Toxins 11, no. 12: 730.

Journal article
Published: 10 December 2019 in Toxins
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Aspergillus flavus is a renowned plant, animal and human pathogen. areA is a global nitrogen regulatory gene of the GATA transcription factor family, shown to be the major nitrogen regulator. In this study, we identified areA in A. flavus and studied its function. The AreA protein contained a signatory zinc finger domain, which is extremely conserved across fungal species. Gene deletion (ΔareA) and over-expression (OE::areA) strains were constructed by homologous recombination to elucidate the role of areA in A. flavus. The ΔareA strain was unable to efficiently utilize secondary nitrogen sources for growth of A. flavus, and it had poorly developed conidiophores, when observed on complete medium, resulting in the production of significantly less conidia than the wild-type strain (WT). Aflatoxin B1 (AFB1) production was reduced in ΔareA compared with the WT strain in most conditions tested, and ΔareA had impaired virulence in peanut seeds. areA also played important roles in the sensitivity of A. flavus to osmotic, cell wall and oxidative stresses. Hence, areA was found to be important for the growth, aflatoxin production and pathogenicity of A. flavus. This work sheds light on the function of areA in the regulation of the nitrogen metabolism of A. flavus, and consequently aims at providing new ways for controlling the crossover pathogen, A. flavus.

ACS Style

Opemipo Esther Fasoyin; Kunlong Yang; Mengguang Qiu; Bin Wang; Sen Wang; Shihua Wang. Regulation of Morphology, Aflatoxin Production, and Virulence of Aspergillus flavus by the Major Nitrogen Regulatory Gene areA. Toxins 2019, 11, 718 .

AMA Style

Opemipo Esther Fasoyin, Kunlong Yang, Mengguang Qiu, Bin Wang, Sen Wang, Shihua Wang. Regulation of Morphology, Aflatoxin Production, and Virulence of Aspergillus flavus by the Major Nitrogen Regulatory Gene areA. Toxins. 2019; 11 (12):718.

Chicago/Turabian Style

Opemipo Esther Fasoyin; Kunlong Yang; Mengguang Qiu; Bin Wang; Sen Wang; Shihua Wang. 2019. "Regulation of Morphology, Aflatoxin Production, and Virulence of Aspergillus flavus by the Major Nitrogen Regulatory Gene areA." Toxins 11, no. 12: 718.

Journal article
Published: 01 October 2019 in Bioorganic Chemistry
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Previous study demonstrated large scale production of trichochecenes which limited the discovery of novel metabolites in Trichoderma hypoxylon. By genetic deletion of trichothecene synthase encoding gene thtri5, we created the dereplication mutant which eliminated the production of trichothecenes. Through chemical isolation, we characterized a couple of rare new polycyclic lactones tricholactones A and B from the thtri5 deletion strain. The structures of these two compounds were well determined by NMR, HR-ESI-MS and IECD analysis.

ACS Style

Lin Chen; Hongbo Wu; Huan Liu; Erwei Li; Jinwei Ren; Wenzhao Wang; Shihua Wang; Wen-Bing Yin. Genetic dereplication of Trichoderma hypoxylon reveals two novel polycyclic lactones. Bioorganic Chemistry 2019, 91, 103185 .

AMA Style

Lin Chen, Hongbo Wu, Huan Liu, Erwei Li, Jinwei Ren, Wenzhao Wang, Shihua Wang, Wen-Bing Yin. Genetic dereplication of Trichoderma hypoxylon reveals two novel polycyclic lactones. Bioorganic Chemistry. 2019; 91 ():103185.

Chicago/Turabian Style

Lin Chen; Hongbo Wu; Huan Liu; Erwei Li; Jinwei Ren; Wenzhao Wang; Shihua Wang; Wen-Bing Yin. 2019. "Genetic dereplication of Trichoderma hypoxylon reveals two novel polycyclic lactones." Bioorganic Chemistry 91, no. : 103185.

Research article
Published: 01 September 2019 in Molecular Plant-Microbe Interactions®
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Histone deacetylases (HDACs) always function as corepressors and sometimes as coactivators in the regulation of fungal development and secondary metabolite production. However, the mechanism through which HDACs play positive roles in secondary metabolite production is still unknown. Here, classical HDAC enzymes were identified and analyzed in Aspergillus flavus, a fungus that produces one of the most carcinogenic secondary metabolites, aflatoxin B1 (AFB1). Characterization of the HDACs revealed that a class I family HDAC, HosA, played crucial roles in growth, reproduction, the oxidative stress response, AFB1 biosynthesis, and pathogenicity. To a lesser extent, a class II family HDAC, HdaA, was also involved in sclerotia formation and AFB1 biosynthesis. An in vitro analysis of HosA revealed that its HDAC activity was considerably diminished at nanomolar concentrations of trichostatin A. Notably, chromatin immunoprecipitation experiments indicated that HosA bound directly to AFB1 biosynthesis cluster genes to regulate their expression. Finally, we found that a transcriptional regulator, SinA, interacts with HosA to regulate fungal development and AFB1 biosynthesis. Overall, our results reveal a novel mechanism by which classical HDACs mediate the induction of secondary metabolite genes in fungi.

ACS Style

Huahui Lan; Lianghuan Wu; Ruilin Sun; Nancy P. Keller; Kunlong Yang; Liuqing Ye; Shuibin He; Feng Zhang; Shihua Wang. The HosA Histone Deacetylase Regulates Aflatoxin Biosynthesis Through Direct Regulation of Aflatoxin Cluster Genes. Molecular Plant-Microbe Interactions® 2019, 32, 1210 -1228.

AMA Style

Huahui Lan, Lianghuan Wu, Ruilin Sun, Nancy P. Keller, Kunlong Yang, Liuqing Ye, Shuibin He, Feng Zhang, Shihua Wang. The HosA Histone Deacetylase Regulates Aflatoxin Biosynthesis Through Direct Regulation of Aflatoxin Cluster Genes. Molecular Plant-Microbe Interactions®. 2019; 32 (9):1210-1228.

Chicago/Turabian Style

Huahui Lan; Lianghuan Wu; Ruilin Sun; Nancy P. Keller; Kunlong Yang; Liuqing Ye; Shuibin He; Feng Zhang; Shihua Wang. 2019. "The HosA Histone Deacetylase Regulates Aflatoxin Biosynthesis Through Direct Regulation of Aflatoxin Cluster Genes." Molecular Plant-Microbe Interactions® 32, no. 9: 1210-1228.

Journal article
Published: 01 August 2019 in Journal of Biological Chemistry
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The fundamental biological function of nucleoside diphosphate kinase (NDK) is to catalyze the reversible exchange of the γ-phosphate between nucleoside triphosphate (NTP) and nucleoside diphosphate (NDP). This kinase also has functions that extend beyond its canonically defined enzymatic role as a phosphotransferase. However, the role of NDK in filamentous fungi, especially in Aspergillus flavus (A. flavus), is not yet known. Here we report that A. flavus has two NDK-encoding gene copies as assessed by qPCR. Using gene-knockout and complementation experiments, we found that AfNDK regulates spore and sclerotia development and is involved in plant virulence as assessed in corn and peanut seed-based assays. An antifungal test with the inhibitor azidothymidine suppressed AfNDK activity in vitro and prevented spore production and sclerotia formation in A. flavus, confirming AfNDK's regulatory functions. Crystallographic analysis of AfNDK, coupled with site-directed mutagenesis experiments, revealed three residues (Arg-104, His-117, and Asp-120) as key sites that contribute to spore and sclerotia development. These results not only enrich our knowledge of the regulatory role of this important protein in A. flavus, but also provide insights into the prevention of A. flavus infection in plants and seeds, as well as into the structural features relevant for future antifungal drug development.

ACS Style

Yu Wang; Sen Wang; Xinyi Nie; Kunlong Yang; Peng Xu; Xiuna Wang; Mengxin Liu; Yongshuai Yang; Zhuo Chen; Shihua Wang. Molecular and structural basis of nucleoside diphosphate kinase–mediated regulation of spore and sclerotia development in the fungus Aspergillus flavus. Journal of Biological Chemistry 2019, 294, 12415 -12431.

AMA Style

Yu Wang, Sen Wang, Xinyi Nie, Kunlong Yang, Peng Xu, Xiuna Wang, Mengxin Liu, Yongshuai Yang, Zhuo Chen, Shihua Wang. Molecular and structural basis of nucleoside diphosphate kinase–mediated regulation of spore and sclerotia development in the fungus Aspergillus flavus. Journal of Biological Chemistry. 2019; 294 (33):12415-12431.

Chicago/Turabian Style

Yu Wang; Sen Wang; Xinyi Nie; Kunlong Yang; Peng Xu; Xiuna Wang; Mengxin Liu; Yongshuai Yang; Zhuo Chen; Shihua Wang. 2019. "Molecular and structural basis of nucleoside diphosphate kinase–mediated regulation of spore and sclerotia development in the fungus Aspergillus flavus." Journal of Biological Chemistry 294, no. 33: 12415-12431.

Journal article
Published: 10 June 2019 in Journal of Hazardous Materials
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ω-conotoxin MVIIA(ω-CTX MVIIA) is a peptide consisting of 25 amino acid residues secreted mainly by Conus magus. In view of the toxin threat to humans and animals and defined application in analgesic therapy, it is necessary to develop a rapid, effective and accuracy method for the quantification and analysis of ω-CTX MVIIA in real samples. In the present study, a hybridoma cell named 2E5 stable secreting IgG antibody against ω-CTX MVIIA was selected successfully, and the subtype of Mab 2E5 was IgG1. The purified monoclonal antibody(Mab) 2E5 has high affinity (about 2.79 × 109 L/mol), and shows high specificity to ω-CTX MVIIA antigen. The linear range of ic-ELISA to detect ω-CTX MVIIA was 0.20˜7.22 μg/mL, with a lower detection limit (LOD) of 0.14 ng/mL. The average recovery of intra- and inter-assay were (85.45 ± 2.28)% and (88.03 ± 4.80)% respectively, with a coefficient of variation from 2.59% to 5.42%. The LOD of colloidal strip by naked eye was 1 μg/mL, and the detection time was less than 10 min without any equipment. The developed ELISA and colloidal test strips based on this IgG antibody could be used to detect ω-CTX MVIIA residue in real Conus samples.

ACS Style

Rongzhi Wang; Yanfang Zhong; Juncheng Wang; Hang Yang; Jun Yuan; Shihua Wang. Development of an ic-ELISA and immunochromatographic strip based on IgG antibody for detection of ω-conotoxin MVIIA. Journal of Hazardous Materials 2019, 378, 120510 .

AMA Style

Rongzhi Wang, Yanfang Zhong, Juncheng Wang, Hang Yang, Jun Yuan, Shihua Wang. Development of an ic-ELISA and immunochromatographic strip based on IgG antibody for detection of ω-conotoxin MVIIA. Journal of Hazardous Materials. 2019; 378 ():120510.

Chicago/Turabian Style

Rongzhi Wang; Yanfang Zhong; Juncheng Wang; Hang Yang; Jun Yuan; Shihua Wang. 2019. "Development of an ic-ELISA and immunochromatographic strip based on IgG antibody for detection of ω-conotoxin MVIIA." Journal of Hazardous Materials 378, no. : 120510.

Journal article
Published: 05 May 2019 in International Journal of Molecular Sciences
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Aspergillus flavus, a ubiquitous filamentous fungus found in soil, plants and other substrates has been reported not only as a pathogen for plants, but also a carcinogen producing fungus for human. Peptidyl-Prolyl Isomerase (PPIases) plays an important role in cell process such as protein secretion cell cycle control and RNA processing. However, the function of PPIase has not yet been identified in A. flavus. In this study, the PPIases gene from A. flavus named ppci1 was cloned into expression vector and the protein was expressed in prokaryotic expression system. Activity of recombinant ppci1 protein was particularly inhibited by FK506, CsA and rapamycin. 3D-Homology model of ppci1 has been constructed with the template, based on 59.7% amino acid similarity. The homologous recombination method was used to construct the single ppci1 gene deletion strain Δppci1. We found that, the ppci1 gene plays important roles in A. flavus growth, conidiation, and sclerotia formation, all of which showed reduction in Δppci1 and increased in conidiation compared with the wild-type and complementary strains in A. flavus. Furthermore, aflatoxin and peanut seeds infection assays indicated that ppci1 contributes to virulence of A. flavus. Furthermore, we evaluated the effect of PPIase inhibitors on A. flavus growth, whereby these were used to treat wild-type strains. We found that the growths were inhibited under every inhibitor. All, these results may provide valuable information for designing inhibitors in the controlling infections of A. flavus.

ACS Style

Saleem Ahmad; Sen Wang; Weizhong Wu; Kunlong Yang; Yan Feng Zhang; Elisabeth Tumukunde; Shihua Wang; Yu Wang. Functional Analysis of Peptidyl-prolyl cis-trans Isomerase from Aspergillus flavus. International Journal of Molecular Sciences 2019, 20, 2206 .

AMA Style

Saleem Ahmad, Sen Wang, Weizhong Wu, Kunlong Yang, Yan Feng Zhang, Elisabeth Tumukunde, Shihua Wang, Yu Wang. Functional Analysis of Peptidyl-prolyl cis-trans Isomerase from Aspergillus flavus. International Journal of Molecular Sciences. 2019; 20 (9):2206.

Chicago/Turabian Style

Saleem Ahmad; Sen Wang; Weizhong Wu; Kunlong Yang; Yan Feng Zhang; Elisabeth Tumukunde; Shihua Wang; Yu Wang. 2019. "Functional Analysis of Peptidyl-prolyl cis-trans Isomerase from Aspergillus flavus." International Journal of Molecular Sciences 20, no. 9: 2206.