scholarly journals Two Histone Deacetylases, FfHda1 and FfHda2, Are Important for Fusarium fujikuroi Secondary Metabolism and Virulence

2013 ◽  
Vol 79 (24) ◽  
pp. 7719-7734 ◽  
Author(s):  
L. Studt ◽  
F. J. Schmidt ◽  
L. Jahn ◽  
C. M. K. Sieber ◽  
L. R. Connolly ◽  
...  
Keyword(s):  
Secondary Metabolism ◽  
Secondary Metabolite ◽  
Filamentous Fungi ◽  
Histone Deacetylases ◽  
Control Plant ◽  
Gene Clusters ◽  
Phytopathogenic Fungus ◽  
Fusarium Fujikuroi ◽  
Content Type ◽  
Encoding Genes

ABSTRACTHistone modifications are crucial for the regulation of secondary metabolism in various filamentous fungi. Here we studied the involvement of histone deacetylases (HDACs) in secondary metabolism in the phytopathogenic fungusFusarium fujikuroi, a known producer of several secondary metabolites, including phytohormones, pigments, and mycotoxins. Deletion of three Zn2+-dependent HDAC-encoding genes,ffhda1,ffhda2, andffhda4, indicated that FfHda1 and FfHda2 regulate secondary metabolism, whereas FfHda4 is involved in developmental processes but is dispensable for secondary-metabolite production inF. fujikuroi. Single deletions offfhda1andffhda2resulted not only in an increase or decrease but also in derepression of metabolite biosynthesis under normally repressing conditions. Moreover, double deletion of both theffhda1andffhda2genes showed additive but also distinct phenotypes with regard to secondary-metabolite biosynthesis, and both genes are required for gibberellic acid (GA)-induced bakanae disease on the preferred host plant rice, as Δffhda1Δffhda2mutants resemble the uninfected control plant. Microarray analysis with a Δffhda1mutant that has lost the major HDAC revealed differential expression of secondary-metabolite gene clusters, which was subsequently verified by a combination of chemical and biological approaches. These results indicate that HDACs are involved not only in gene silencing but also in the activation of some genes. Chromatin immunoprecipitation with the Δffhda1mutant revealed significant alterations in the acetylation state of secondary-metabolite gene clusters compared to the wild type, thereby providing insights into the regulatory mechanism at the chromatin level. Altogether, manipulation of HDAC-encoding genes constitutes a powerful tool to control secondary metabolism in filamentous fungi.

scholarly journals Transcriptome Analysis of Aspergillus flavus RevealsveA-Dependent Regulation of Secondary Metabolite Gene Clusters, Including the Novel Aflavarin Cluster

2015 ◽  
Vol 14 (10) ◽  
pp. 983-997 ◽  
Author(s):  
J. W. Cary ◽  
Z. Han ◽  
Y. Yin ◽  
J. M. Lohmar ◽  
S. Shantappa ◽  
...  
Keyword(s):  
Secondary Metabolism ◽  
Secondary Metabolite ◽  
Aspergillus Flavus ◽  
Gene Clusters ◽  
Fungal Species ◽  
The Novel ◽  
Content Type ◽  
Expression Of Genes ◽  
Number Of Genes ◽  
Fungal Secondary Metabolism

ABSTRACTThe global regulatoryveAgene governs development and secondary metabolism in numerous fungal species, includingAspergillus flavus. This is especially relevant sinceA. flavusinfects crops of agricultural importance worldwide, contaminating them with potent mycotoxins. The most well-known are aflatoxins, which are cytotoxic and carcinogenic polyketide compounds. The production of aflatoxins and the expression of genes implicated in the production of these mycotoxins areveAdependent. The genes responsible for the synthesis of aflatoxins are clustered, a signature common for genes involved in fungal secondary metabolism. Studies of theA. flavusgenome revealed many gene clusters possibly connected to the synthesis of secondary metabolites. Many of these metabolites are still unknown, or the association between a known metabolite and a particular gene cluster has not yet been established. In the present transcriptome study, we show thatveAis necessary for the expression of a large number of genes. Twenty-eight out of the predicted 56 secondary metabolite gene clusters include at least one gene that is differentially expressed depending on presence or absence ofveA. One of the clusters under the influence ofveAis cluster 39. The absence ofveAresults in a downregulation of the five genes found within this cluster. Interestingly, our results indicate that the cluster is expressed mainly in sclerotia. Chemical analysis of sclerotial extracts revealed that cluster 39 is responsible for the production of aflavarin.

scholarly journals Light-Dependent Functions of the Fusarium fujikuroi CryD DASH Cryptochrome in Development and Secondary Metabolism

2013 ◽  
Vol 79 (8) ◽  
pp. 2777-2788 ◽  
Author(s):  
Marta Castrillo ◽  
Jorge García-Martínez ◽  
Javier Avalos
Keyword(s):  
Secondary Metabolism ◽  
Nitrogen Starvation ◽  
Phytopathogenic Fungus ◽  
Fusarium Fujikuroi ◽  
Mrna Levels ◽  
Wild Type ◽  
Gene Encoding ◽  
Content Type ◽  
Gibberellin Production ◽  
In The Wild

ABSTRACTDASH (Drosophila,Arabidopsis,Synechocystis, human) cryptochromes (cry-DASHs) constitute a subgroup of the photolyase cryptochrome family with diverse light-sensing roles, found in most taxonomical groups. The genome ofFusarium fujikuroi, a phytopathogenic fungus with a rich secondary metabolism, contains a gene encoding a putative cry-DASH, named CryD. The expression of thecryDgene is induced by light in the wild type, but not in mutants of the “white collar” genewcoA. Targeted ΔcryDmutants show light-dependent phenotypic alterations, including changes in morphology and pigmentation, which disappear upon reintroduction of a wild-typecryDallele. In addition to microconidia, the colonies of the ΔcryDmutants produced under illumination and nitrogen starvation large septated spores called macroconidia, absent in wild-type colonies. The ΔcryDmutants accumulated similar amounts of carotenoids to the control strain under constant illumination, but produced much larger amounts of bikaverin under nitrogen starvation, indicating a repressing role for CryD in this biosynthetic pathway. Additionally, a moderate photoinduction of gibberellin production was exhibited by the wild type but not by the ΔcryDmutants. The phenotypic alterations of the ΔcryDmutants were only noticeable in the light, as expected from the low expression ofcryDin the dark, but did not correlate with mRNA levels for structural genes of the bikaverin or gibberellin biosynthetic pathways, suggesting the participation of CryD in posttranscriptional regulatory mechanisms. This is the first report on the participation of a cry-DASH protein in the regulation of fungal secondary metabolism.

scholarly journals Transcriptomic, Protein-DNA Interaction, and Metabolomic Studies of VosA, VelB, and WetA in Aspergillus nidulans Asexual Spores

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming-Yueh Wu ◽  
Matthew E. Mead ◽  
Mi-Kyung Lee ◽  
George F. Neuhaus ◽  
Donovon A. Adpressa ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Secondary Metabolism ◽  
Aspergillus Nidulans ◽  
Filamentous Fungi ◽  
Genetic Regulatory Networks ◽  
Asexual Development ◽  
Morphological Development ◽  
Vast Number ◽  
Content Type ◽  
Metabolic Remodeling

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.

scholarly journals Phylogenetic Distribution of Secondary Metabolites in the Bacillus subtilis Species Complex

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Kat Steinke ◽  
Omkar S. Mohite ◽  
Tilmann Weber ◽  
Ákos T. Kovács
Keyword(s):  
Bacillus Subtilis ◽  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Species Complex ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Content Type ◽  
Frameshift Mutations ◽  
Metabolite Production

ABSTRACT Microbes produce a plethora of secondary (or specialized) metabolites that, although not essential for primary metabolism, benefit them to survive in the environment, communicate, and influence cell differentiation. Biosynthetic gene clusters (BGCs), responsible for the production of these secondary metabolites, are readily identifiable on bacterial genome sequences. Understanding the phylogeny and distribution of BGCs helps us to predict the natural product synthesis ability of new isolates. Here, we examined 310 genomes from the Bacillus subtilis group, determined the inter- and intraspecies patterns of absence/presence for all BGCs, and assigned them to defined gene cluster families (GCFs). This allowed us to establish patterns in the distribution of both known and unknown products. Further, we analyzed variations in the BGC structures of particular families encoding natural products, such as plipastatin, fengycin, iturin, mycosubtilin, and bacillomycin. Our detailed analysis revealed multiple GCFs that are species or clade specific and a few others that are scattered within or between species, which will guide exploration of the chemodiversity within the B. subtilis group. Surprisingly, we discovered that partial deletion of BGCs and frameshift mutations in selected biosynthetic genes are conserved within phylogenetically related isolates, although isolated from around the globe. Our results highlight the importance of detailed genomic analysis of BGCs and the remarkable phylogenetically conserved erosion of secondary metabolite biosynthetic potential in the B. subtilis group. IMPORTANCE Members of the B. subtilis species complex are commonly recognized producers of secondary metabolites, among those, the production of antifungals, which makes them promising biocontrol strains. While there are studies examining the distribution of well-known secondary metabolites in Bacilli, intraspecies clade-specific distribution has not been systematically reported for the B. subtilis group. Here, we report the complete biosynthetic potential within the B. subtilis group to explore the distribution of the biosynthetic gene clusters and to reveal an exhaustive phylogenetic conservation of secondary metabolite production within Bacillus that supports the chemodiversity within this species complex. We identify that certain gene clusters acquired deletions of genes and particular frameshift mutations, rendering them inactive for secondary metabolite biosynthesis, a conserved genetic trait within phylogenetically conserved clades of certain species. The overview guides the assignment of the secondary metabolite production potential of newly isolated Bacillus strains based on genome sequence and phylogenetic relatedness.

scholarly journals Elucidating the Regulatory Elements for Transcription Termination and Posttranscriptional Processing in the Streptomyces clavuligerus Genome

mSystems ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Soonkyu Hwang ◽  
Namil Lee ◽  
Donghui Choe ◽  
Yongjae Lee ◽  
Woori Kim ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Transcription Termination ◽  
Gene Clusters ◽  
Streptomyces Clavuligerus ◽  
Regulatory Elements ◽  
Regulation Of Transcription ◽  
Content Type ◽  
Transcriptional Regulatory Elements ◽  
Transcriptional Regulatory ◽  
Posttranscriptional Processing

ABSTRACT Identification of transcriptional regulatory elements in the GC-rich Streptomyces genome is essential for the production of novel biochemicals from secondary metabolite biosynthetic gene clusters (smBGCs). Despite many efforts to understand the regulation of transcription initiation in smBGCs, information on the regulation of transcription termination and posttranscriptional processing remains scarce. In this study, we identified the transcriptional regulatory elements in β-lactam antibiotic-producing Streptomyces clavuligerus ATCC 27064 by determining a total of 1,427 transcript 3′-end positions (TEPs) using the term-seq method. Termination of transcription was governed by three classes of TEPs, of which each displayed unique sequence features. The data integration with transcription start sites and transcriptome data generated 1,648 transcription units (TUs) and 610 transcription unit clusters (TUCs). TU architecture showed that the transcript abundance in TU isoforms of a TUC was potentially affected by the sequence context of their TEPs, suggesting that the regulatory elements of TEPs could control the transcription level in additional layers. We also identified TU features of a xenobiotic response element (XRE) family regulator and DUF397 domain-containing protein, particularly showing the abundance of bidirectional TEPs. Finally, we found that 189 noncoding TUs contained potential cis- and trans-regulatory elements that played a major role in regulating the 5′ and 3′ UTR. These findings highlight the role of transcriptional regulatory elements in transcription termination and posttranscriptional processing in Streptomyces sp. IMPORTANCE Streptomyces sp. is a great source of bioactive secondary metabolites, including antibiotics, antifungal agents, antiparasitic agents, immunosuppressant compounds, and other drugs. Secondary metabolites are synthesized via multistep conversions of the precursor molecules from primary metabolism, governed by multicomplex enzymes from secondary metabolite biosynthetic gene clusters. As their production is closely related with the growth phase and dynamic cellular status in response to various intra- and extracellular signals, complex regulatory systems tightly control the gene expressions related to secondary metabolism. In this study, we determined genome-wide transcript 3′-end positions and transcription units in the β-lactam antibiotic producer Streptomyces clavuligerus ATCC 27064 to elucidate the transcriptional regulatory elements in transcription termination and posttranscriptional processing by integration of multiomics data. These unique features, such as transcript 3′-end sequence, potential riboregulators, and potential 3′-untranslated region (UTR) cis-regulatory elements, can be potentially used to design engineering tools that can regulate the transcript abundance of genes for enhancing secondary metabolite production.

scholarly journals Diversity of Secondary Metabolism in Aspergillus nidulans Clinical Isolates

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
M. T. Drott ◽  
R. W. Bastos ◽  
A. Rokas ◽  
L. N. A. Ries ◽  
T. Gabaldón ◽  
...  
Keyword(s):  
Secondary Metabolism ◽  
Aspergillus Nidulans ◽  
Reference Genome ◽  
Genetic Model ◽  
High Resolution Mass Spectrometry ◽  
Gene Clusters ◽  
Clinical Isolates ◽  
Biosynthetic Gene ◽  
Content Type ◽  
Natural Diversity

ABSTRACT The filamentous fungus Aspergillus nidulans has been a primary workhorse used to understand fungal genetics. Much of this work has focused on elucidating the genetics of biosynthetic gene clusters (BGCs) and the secondary metabolites (SMs) they produce. SMs are both niche defining in fungi and of great economic importance to humans. Despite the focus on A. nidulans, very little is known about the natural diversity in secondary metabolism within this species. We determined the BGC content and looked for evolutionary patterns in BGCs from whole-genome sequences of two clinical isolates and the A4 reference genome of A. nidulans. Differences in BGC content were used to explain SM profiles determined using liquid chromatography–high-resolution mass spectrometry. We found that in addition to genetic variation of BGCs contained by all isolates, nine BGCs varied by presence/absence. We discovered the viridicatumtoxin BGC in A. nidulans and suggest that this BGC has undergone a horizontal gene transfer from the Aspergillus section Nigri lineage into Penicillium sometime after the sections Nigri and Nidulantes diverged. We identified the production of viridicatumtoxin and several other compounds previously not known to be produced by A. nidulans. One isolate showed a lack of sterigmatocystin production even though it contained an apparently intact sterigmatocystin BGC, raising questions about other genes and processes known to regulate this BGC. Altogether, our work uncovers a large degree of intraspecies diversity in BGC and SM production in this genetic model species and offers new avenues to understand the evolution and regulation of secondary metabolism. IMPORTANCE Much of what we know about the genetics underlying secondary metabolite (SM) production and the function of SMs in the model fungus Aspergillus nidulans comes from a single reference genome. A growing body of research indicates the importance of biosynthetic gene cluster (BGC) and SM diversity within a species. However, there is no information about the natural diversity of secondary metabolism in A. nidulans. We discovered six novel clusters that contribute to the considerable variation in both BGC content and SM production within A. nidulans. We characterize a diverse set of mutations and emphasize how findings of single nucleotide polymorphisms (SNPs), deletions, and differences in evolutionary history encompass much of the variation observed in nonmodel systems. Our results emphasize that A. nidulans may also be a strong model to use within-species diversity to elucidate regulatory cross talk, fungal ecology, and drug discovery systems.

scholarly journals Comparative Transcriptome Analysis Shows Conserved Metabolic Regulation during Production of Secondary Metabolites in Filamentous Fungi

mSystems ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Jens Christian Nielsen ◽  
Sylvain Prigent ◽  
Sietske Grijseels ◽  
Mhairi Workman ◽  
Boyang Ji ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Secondary Metabolite ◽  
Filamentous Fungi ◽  
Metabolic Regulation ◽  
Fungal Species ◽  
Efficient Production ◽  
Fungal Cell ◽  
Fungal Metabolism ◽  
Cell Factories

ABSTRACTFilamentous fungi possess great potential as sources of medicinal bioactive compounds, such as antibiotics, but efficient production is hampered by a limited understanding of how their metabolism is regulated. We investigated the metabolism of six secondary metabolite-producing fungi of thePenicilliumgenus during nutrient depletion in the stationary phase of batch fermentations and assessed conserved metabolic responses across species using genome-wide transcriptional profiling. A coexpression analysis revealed that expression of biosynthetic genes correlates with expression of genes associated with pathways responsible for the generation of precursor metabolites for secondary metabolism. Our results highlight the main metabolic routes for the supply of precursors for secondary metabolism and suggest that the regulation of fungal metabolism is tailored to meet the demands for secondary metabolite production. These findings can aid in identifying fungal species that are optimized for the production of specific secondary metabolites and in designing metabolic engineering strategies to develop high-yielding fungal cell factories for production of secondary metabolites.IMPORTANCESecondary metabolites are a major source of pharmaceuticals, especially antibiotics. However, the development of efficient processes of production of secondary metabolites has proved troublesome due to a limited understanding of the metabolic regulations governing secondary metabolism. By analyzing the conservation in gene expression across secondary metabolite-producing fungal species, we identified a metabolic signature that links primary and secondary metabolism and that demonstrates that fungal metabolism is tailored for the efficient production of secondary metabolites. The insight that we provide can be used to develop high-yielding fungal cell factories that are optimized for the production of specific secondary metabolites of pharmaceutical interest.

scholarly journals Characterizing the Pathogenic, Genomic, and Chemical Traits ofAspergillus fischeri, a Close Relative of the Major Human Fungal PathogenAspergillus fumigatus

mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Matthew E. Mead ◽  
Sonja L. Knowles ◽  
Huzefa A. Raja ◽  
Sarah R. Beattie ◽  
Caitlin H. Kowalski ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Aspergillus Fumigatus ◽  
Secondary Metabolism ◽  
Human Disease ◽  
Chemical Characterization ◽  
Gene Clusters ◽  
Invasive Disease ◽  
Close Relative ◽  
Low Oxygen ◽  
Content Type

ABSTRACTAspergillus fischeriis closely related toAspergillus fumigatus, the major cause of invasive mold infections. Even thoughA. fischeriis commonly found in diverse environments, including hospitals, it rarely causes invasive disease. WhyA. fischericauses less human disease thanA. fumigatusis unclear. A comparison ofA. fischeriandA. fumigatusfor pathogenic, genomic, and secondary metabolic traits revealed multiple differences in pathogenesis-related phenotypes. We observed thatA. fischeriNRRL 181 is less virulent thanA. fumigatusstrain CEA10 in multiple animal models of disease, grows slower in low-oxygen environments, and is more sensitive to oxidative stress. Strikingly, the observed differences for some traits are of the same order of magnitude as those previously reported betweenA. fumigatusstrains. In contrast, similar to what has previously been reported, the two species exhibit high genomic similarity; ∼90% of theA. fumigatusproteome is conserved inA. fischeri, including 48/49 genes known to be involved inA. fumigatusvirulence. However, only 10/33A. fumigatusbiosynthetic gene clusters (BGCs) likely involved in secondary metabolite production are conserved inA. fischeriand only 13/48A. fischeriBGCs are conserved inA. fumigatus. Detailed chemical characterization ofA. fischericultures grown on multiple substrates identified multiple secondary metabolites, including two new compounds and one never before isolated as a natural product. Additionally, anA. fischerideletion mutant oflaeA, a master regulator of secondary metabolism, produced fewer secondary metabolites and in lower quantities, suggesting that regulation of secondary metabolism is at least partially conserved. These results suggest that the nonpathogenicA. fischeripossesses many of the genes important forA. fumigatuspathogenicity but is divergent with respect to its ability to thrive under host-relevant conditions and its secondary metabolism.IMPORTANCEAspergillus fumigatusis the primary cause of aspergillosis, a devastating ensemble of diseases associated with severe morbidity and mortality worldwide.A. fischeriis a close relative ofA. fumigatusbut is not generally observed to cause human disease. To gain insights into the underlying causes of this remarkable difference in pathogenicity, we compared two representative strains (one from each species) for a range of pathogenesis-relevant biological and chemical characteristics. We found that disease progression in multipleA. fischerimouse models was slower and caused less mortality thanA. fumigatus. Remarkably, the observed differences betweenA. fischeriandA. fumigatusstrains examined here closely resembled those previously described for two commonly studiedA. fumigatusstrains, AF293 and CEA10.A. fischeriandA. fumigatusexhibited different growth profiles when placed in a range of stress-inducing conditions encountered during infection, such as low levels of oxygen and the presence of chemicals that induce the production of reactive oxygen species. We also found that the vast majority ofA. fumigatusgenes known to be involved in virulence are conserved inA. fischeri, whereas the two species differ significantly in their secondary metabolic pathways. These similarities and differences that we report here are the first step toward understanding the evolutionary origin of a major fungal pathogen.

scholarly journals A Novel AdpA Homologue Negatively Regulates Morphological Differentiation inStreptomyces xiamenensis318

2019 ◽  
Vol 85 (7) ◽  
Author(s):  
Xu-Liang Bu ◽  
Jing-Yi Weng ◽  
Bei-Bei He ◽  
Min-Juan Xu ◽  
Jun Xu
Keyword(s):  
Cell Growth ◽  
Secondary Metabolism ◽  
Gene Cluster ◽  
Morphological Differentiation ◽  
Gene Clusters ◽  
Transcriptional Level ◽  
Negative Effects ◽  
Promoter Regions ◽  
Content Type ◽  
Enhanced Production

ABSTRACTThe pleiotropic transcriptional regulator AdpA positively controls morphological differentiation and regulates secondary metabolism in mostStreptomycesspecies.Streptomyces xiamenensis318 has a linear chromosome 5.96 Mb in size. How AdpA affects secondary metabolism and morphological differentiation in such a naturally minimized genomic background is unknown. Here, we demonstrated that AdpASx, an AdpA orthologue inS. xiamenensis, negatively regulates cell growth and sporulation and bidirectionally regulates the biosynthesis of xiamenmycin and polycyclic tetramate macrolactams (PTMs) inS. xiamenensis318. Overexpression of theadpASxgene inS. xiamenensis318 had negative effects on morphological differentiation and resulted in reduced transcription of putativessgA,ftsZ,ftsH,amfC,whiB,wblA1,wblA2,wblE, and a gene encoding sporulation-associated protein (sxim_29740), whereas the transcription of putativebldDandbldAgenes was upregulated. Overexpression ofadpASxled to significantly enhanced production of xiamenmycin but had detrimental effects on the production of PTMs. As expected, the transcriptional level of theximgene cluster was upregulated, whereas the PTM gene cluster was downregulated. Moreover, AdpASxnegatively regulated the transcription of its own gene. Electrophoretic mobility shift assays revealed that AdpASxcan bind the promoter regions of structural genes of both theximand PTM gene clusters as well as to the promoter regions of genes potentially involved in the cell growth and differentiation ofS. xiamenensis318. We report that an AdpA homologue has negative effects on morphological differentiation inS. xiamenensis318, a finding confirmed when AdpASxwas introduced into the heterologous hostStreptomyces lividansTK24.IMPORTANCEAdpA is a key regulator of secondary metabolism and morphological differentiation inStreptomycesspecies. However, AdpA had not been reported to negatively regulate morphological differentiation. Here, we characterized the regulatory role of AdpASxinStreptomyces xiamenensis318, which has a naturally streamlined genome. In this strain, AdpASxnegatively regulated cell growth and morphological differentiation by directly controlling genes associated with these functions. AdpASxalso bidirectionally controlled the biosynthesis of xiamenmycin and PTMs by directly regulating their gene clusters rather than through other regulators. Our findings provide additional evidence for the versatility of AdpA in regulating morphological differentiation and secondary metabolism inStreptomyces.

Sign in / Sign up

Export Citation Format

Share Document