scholarly journals Hormonal control by A-factor of morphological development and secondary metabolism in Streptomyces

2007 ◽  
Vol 83 (9/10) ◽  
pp. 277-295 ◽  
Author(s):  
Sueharu HORINOUCHI ◽  
Teruhiko BEPPU
mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming-Yueh Wu ◽  
Matthew E. Mead ◽  
Mi-Kyung Lee ◽  
George F. Neuhaus ◽  
Donovon A. Adpressa ◽  
...  

ABSTRACT In filamentous fungi, asexual development involves cellular differentiation and metabolic remodeling leading to the formation of intact asexual spores. The development of asexual spores (conidia) in Aspergillus is precisely coordinated by multiple transcription factors (TFs), including VosA, VelB, and WetA. Notably, these three TFs are essential for the structural and metabolic integrity, i.e., proper maturation, of conidia in the model fungus Aspergillus nidulans. To gain mechanistic insight into the complex regulatory and interdependent roles of these TFs in asexual sporogenesis, we carried out multi-omics studies on the transcriptome, protein-DNA interactions, and primary and secondary metabolism employing A. nidulans conidia. RNA sequencing and chromatin immunoprecipitation sequencing analyses have revealed that the three TFs directly or indirectly regulate the expression of genes associated with heterotrimeric G-protein signal transduction, mitogen-activated protein (MAP) kinases, spore wall formation and structural integrity, asexual development, and primary/secondary metabolism. In addition, metabolomics analyses of wild-type and individual mutant conidia indicate that these three TFs regulate a diverse array of primary metabolites, including those in the tricarboxylic acid (TCA) cycle, certain amino acids, and trehalose, and secondary metabolites such as sterigmatocystin, emericellamide, austinol, and dehydroaustinol. In summary, WetA, VosA, and VelB play interdependent, overlapping, and distinct roles in governing morphological development and primary/secondary metabolic remodeling in Aspergillus conidia, leading to the production of vital conidia suitable for fungal proliferation and dissemination. IMPORTANCE Filamentous fungi produce a vast number of asexual spores that act as efficient propagules. Due to their infectious and/or allergenic nature, fungal spores affect our daily life. Aspergillus species produce asexual spores called conidia; their formation involves morphological development and metabolic changes, and the associated regulatory systems are coordinated by multiple transcription factors (TFs). To understand the underlying global regulatory programs and cellular outcomes associated with conidium formation, genomic and metabolomic analyses were performed in the model fungus Aspergillus nidulans. Our results show that the fungus-specific WetA/VosA/VelB TFs govern the coordination of morphological and chemical developments during sporogenesis. The results of this study provide insights into the interdependent, overlapping, or distinct genetic regulatory networks necessary to produce intact asexual spores. The findings are relevant for other Aspergillus species such as the major human pathogen Aspergillus fumigatus and the aflatoxin producer Aspergillus flavus.


2012 ◽  
Vol 78 (22) ◽  
pp. 8015-8024 ◽  
Author(s):  
Aiyada Aroonsri ◽  
Shigeru Kitani ◽  
Junko Hashimoto ◽  
Ikuko Kosone ◽  
Miho Izumikawa ◽  
...  

ABSTRACTThe γ-butyrolactone autoregulator signaling cascades have been shown to control secondary metabolism and/or morphological development among manyStreptomycesspecies. However, the conservation and variation of the regulatory systems among actinomycetes remain to be clarified. The genome sequence ofKitasatospora setae, which also belongs to the familyStreptomycetaceaecontaining the genusStreptomyces, has revealed the presence of three homologues of the autoregulator receptor: KsbA, which has previously been confirmed to be involved only in secondary metabolism; KsbB; and KsbC. We describe here the characterization ofksbC, whose regulatory cluster closely resembles theStreptomyces virginiae barAlocus responsible for the autoregulator signaling cascade. Deletion of the geneksbCresulted in lowered production of bafilomycin and a defect of aerial mycelium formation, together with the early and enhanced production of a novel β-carboline alkaloid named kitasetaline. A putative kitasetaline biosynthetic gene cluster was identified, and its expression in a heterologous host led to the production of kitasetaline together with JBIR-133, the production of which is also detected in theksbCdisruptant, and JBIR-134 as novel β-carboline alkaloids, indicating that these genes were biosynthetic genes for β-carboline alkaloid and thus are the first such genes to be discovered in bacteria.


Biofilms ◽  
2004 ◽  
Vol 1 (4) ◽  
pp. 319-328 ◽  
Author(s):  
Y. Ohnishi ◽  
S. Horinouchi

A-factor (2-isocapryloyl-3R-hydroxymethyl-γ-butyrolactone) is a chemical signalling molecule, or microbial hormone, that triggers aerial mycelium formation and secondary metabolism in Streptomyces griseus. A-factor pro- duced in a growth-dependent manner switches on the transcription of adpA, encoding a transcriptional activator, by binding to ArpA, the A-factor receptor protein, which has bound to the adpA promoter, and dissociating the bound ArpA from the DNA. AdpA then activates a number of genes of various functions required for morphological development and secondary metabolism, forming an AdpA regulon. ArpA, which belongs to the TetR family, contains a helix–turn–helix DNA-binding motif in its N-terminal portion and an A-factor-binding pocket (5 Å (0.5 nm) diameter and 20 Å (2 nm) long) in its C-terminal portion, as implied by X-ray crystallography of CprB, an ArpA homologue. The ligand pocket, which can accommodate an entire A-factor-type molecule of γ-butyrolactone, is completely embedded in the C-terminal portion. Upon binding A-factor, a long helix connecting the A-factor-binding and ligand-binding domains is relocated, as a result of which the DNA-binding helix moves outside, resulting in dissociation from DNA. AdpA, which belongs to the AraC/XylS family, contains a ThiJ/PfpI/DJ-1-like dimerization domain in its N-terminal portion and an AraC/XylS-type DNA-binding domain in its C-terminal portion. For transcriptional activation, AdpA can bind to various positions with respect to the transcriptional start points of the target genes and sometimes to multiple sites. We show here how A-factor triggers secondary metabolism and morphological development in S. griseus, with emphasis on the two key transcriptional factors, ArpA and AdpA, in the A-factor regulatory cascade.


2018 ◽  
Vol 365 (17) ◽  
Author(s):  
Ting Lu ◽  
Yanping Zhu ◽  
Peipei Zhang ◽  
Duohong Sheng ◽  
Guangxiang Cao ◽  
...  

2017 ◽  
Vol 84 (5) ◽  
Author(s):  
Beatriz A. Ibarra ◽  
Jessica M. Lohmar ◽  
Timothy Satterlee ◽  
Taylor McDonald ◽  
Jeffrey W. Cary ◽  
...  

ABSTRACTThe opportunistic plant-pathogenic fungusAspergillus flavusproduces carcinogenic mycotoxins termed aflatoxins (AF). Aflatoxin contamination of agriculturally important crops, such as maize, peanut, sorghum, and tree nuts, is responsible for serious adverse health and economic impacts worldwide. In order to identify possible genetic targets to reduce AF contamination, we have characterized theartAgene, encoding a putative 14-3-3 homolog inA. flavus. TheartAdeletion mutant presents a slight decrease in vegetative growth and alterations in morphological development and secondary metabolism. Specifically,artAaffects conidiation, and this effect is influenced by the type of substrate and culture condition. In addition, normal levels ofartAare required for sclerotial development. Importantly,artAnegatively regulates AF production as well as the concomitant expression of genes in the AF gene cluster. An increase in AF is also observed in seeds infected with theA. flavusstrain lackingartA. Furthermore, the expression of other secondary metabolite genes is alsoartAdependent, including genes in the cyclopiazonic acid (CPA) and ustiloxin gene clusters, in this agriculturally important fungus.IMPORTANCEIn the current study,artA, which encodes a 14-3-3 homolog, was characterized in the agriculturally and medically important fungusAspergillus flavus, specifically, its possible role governing sporulation, formation of resistant structures, and secondary metabolism. The highly conservedartAis necessary for normal fungal morphogenesis in an environment-dependent manner, affecting the balance between production of conidiophores and the formation of resistant structures that are necessary for the dissemination and survival of this opportunistic pathogen. This study reports a 14-3-3 protein affecting secondary metabolism in filamentous fungi. Importantly,artAregulates the biosynthesis of the potent carcinogenic compound aflatoxin B1 (AFB1) as well as the production of other secondary metabolites.


2003 ◽  
Vol 2 (6) ◽  
pp. 1178-1186 ◽  
Author(s):  
Naoki Kato ◽  
Wilhelmina Brooks ◽  
Ana M. Calvo

ABSTRACT Secondary metabolism is commonly associated with morphological development in microorganisms, including fungi. We found that veA, a gene previously shown to control the Aspergillus nidulans sexual/asexual developmental ratio in response to light, also controls secondary metabolism. Specifically, veA regulates the expression of genes implicated in the synthesis of the mycotoxin sterigmatocystin and the antibiotic penicillin. veA is necessary for the expression of the transcription factor aflR, which activates the gene cluster that leads to the production of sterigmatocystin. veA is also necessary for penicillin production. Our results indicated that although veA represses the transcription of the isopenicillin synthetase gene ipnA, it is necessary for the expression of acvA, the key gene in the first step of penicillin biosynthesis, encoding the delta-(l-alpha-aminoadipyl)-l-cysteinyl-d-valine synthetase. With respect to the mechanism of veA in directing morphological development, veA has little effect on the expression of the known sexual transcription factors nsdD and steA. However, we found that veA regulates the expression of the asexual transcription factor brlA by modulating the α/β transcript ratio that controls conidiation.


Metallomics ◽  
2016 ◽  
Vol 8 (5) ◽  
pp. 469-480 ◽  
Author(s):  
Fabricio M. Locatelli ◽  
Kian-Sim Goo ◽  
Dana Ulanova

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