scholarly journals The Coordinated Positive Regulation of Topoisomerase Genes Maintains Topological Homeostasis in Streptomyces coelicolor

2016 ◽  
Vol 198 (21) ◽  
pp. 3016-3028 ◽  
Author(s):  
Marcin Jan Szafran ◽  
Martyna Gongerowska ◽  
Paweł Gutkowski ◽  
Jolanta Zakrzewska-Czerwińska ◽  
Dagmara Jakimowicz
Keyword(s):  
Secondary Metabolites ◽  
Topoisomerase I ◽  
Elevated Temperatures ◽  
Antitumor Agents ◽  
Streptomyces Coelicolor ◽  
Optimal Level ◽  
Industrial Applications ◽  
Biologically Active ◽  
Content Type ◽  
Number Of Genes

ABSTRACTMaintaining an optimal level of chromosomal supercoiling is critical for the progression of DNA replication and transcription. Moreover, changes in global supercoiling affect the expression of a large number of genes and play a fundamental role in adapting to stress. Topoisomerase I (TopA) and gyrase are key players in the regulation of bacterial chromosomal topology through their respective abilities to relax and compact DNA. Soil bacteria such asStreptomycesspecies, which grow as branched, multigenomic hyphae, are subject to environmental stresses that are associated with changes in chromosomal topology. The topological fluctuations modulate the transcriptional activity of a large number of genes and inStreptomycesare related to the production of antibiotics. To better understand the regulation of topological homeostasis inStreptomyces coelicolor, we investigated the interplay between the activities of the topoisomerase-encoding genestopAandgyrBA. We show that the expression of both genes is supercoiling sensitive. Remarkably, increased chromosomal supercoiling induces thetopApromoter but only slightly influencesgyrBAtranscription, while DNA relaxation affects thetopApromoter only marginally but strongly activates thegyrBAoperon. Moreover, we showed that exposure to elevated temperatures induces rapid relaxation, which results in changes in the levels of both topoisomerases. We therefore propose a unique mechanism ofS. coelicolorchromosomal topology maintenance based on the supercoiling-dependent stimulation, rather than repression, of the transcription of both topoisomerase genes. These findings provide important insight into the maintenance of topological homeostasis in an industrially important antibiotic producer.IMPORTANCEWe describe the unique regulation of genes encoding two topoisomerases, topoisomerase I (TopA) and gyrase, in a modelStreptomycesspecies. Our studies demonstrate the coordination of topoisomerase gene regulation, which is crucial for maintenance of topological homeostasis.Streptomycesspecies are producers of a plethora of biologically active secondary metabolites, including antibiotics, antitumor agents, and immunosuppressants. The significant regulatory factor controlling the secondary metabolism is the global chromosomal topology. Thus, the investigation of chromosomal topology homeostasis inStreptomycesstrains is crucial for their use in industrial applications as producers of secondary metabolites.

scholarly journals Secondary metabolites of a marine-derived Penicillium ochrochloron

2021 ◽  
Vol 13 (3) ◽  
pp. 11020
Author(s):  
Peter M. EZE ◽  
Ying GAO ◽  
Yang LIU ◽  
Lasse Van GEELEN ◽  
Chika P. EJIKEUGWU ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Secondary Metabolites ◽  
Biological Properties ◽  
Industrial Applications ◽  
Biologically Active ◽  
Fungal Isolation ◽  
The North ◽  
Wide Range ◽  
Extremophilic Fungi ◽  
Fungal Secondary Metabolites

Extremophilic fungi have received considerable attention recently as new promising sources of biologically active compounds with potential pharmaceutical applications. This study investigated the secondary metabolites of a marine-derived Penicillium ochrochloron isolated from underwater sea sand collected from the North Sea in St. Peter-Ording, Germany. Standard techniques were used for fungal isolation, taxonomic identification, fermentation, extraction, and isolation of fungal secondary metabolites. Chromatographic separation and spectroscopic analyses of the fungal secondary metabolites yielded eight compounds: talumarin A (1), aspergillumarin A (2), andrastin A (3), clavatol (4), 3-acetylphenol (5), methyl 2,5-dihydro-4-hydroxy-5-oxo-3-phenyl-2-furanpropanoate (6), emodin (7) and 2-chloroemodin (8). After co-cultivation with Bacillus subtilis, the fungus was induced to express (-)-striatisporolide A (9). Compound 1 was evaluated for antibacterial activity against Staphylococcus aureus, Acinetobacter baumannii, Mycobacterium smegmatis, and M. tuberculosis, as well as cytotoxicity against THP-1 cells. The compound, however, was not cytotoxic to THP-1 cells and had no antibacterial activity against the microorganisms tested. The compounds isolated from P. ochrochloron in this study are well-known compounds with a wide range of beneficial biological properties that can be explored for pharmaceutical, agricultural, or industrial applications. This study highlights the bioprospecting potential of marine fungi and confirms co-cultivation as a useful strategy for the discovery of new natural products.

scholarly journals An IgaA/UmoB Family Protein fromSerratia marcescensRegulates Motility, Capsular Polysaccharide Biosynthesis, and Secondary Metabolite Production

2018 ◽  
Vol 84 (6) ◽  
Author(s):  
Nicholas A. Stella ◽  
Kimberly M. Brothers ◽  
Jake D. Callaghan ◽  
Angelina M. Passerini ◽  
Cihad Sigindere ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Intracellular Signaling ◽  
Biofilm Formation ◽  
Capsular Polysaccharide ◽  
Biologically Active ◽  
Public Health Importance ◽  
Content Type ◽  
Polysaccharide Biosynthesis ◽  
Transcriptional Changes

ABSTRACTSecondary metabolites are an important source of pharmaceuticals and key modulators of microbe-microbe interactions. The bacteriumSerratia marcescensis part of theEnterobacteriaceaefamily of eubacteria and produces a number of biologically active secondary metabolites. In this study, we screened for novel regulators of secondary metabolites synthesized by a clinical isolate ofS. marcescensand found mutations in a gene for an uncharacterized UmoB/IgaA family member here namedgumB. Mutation ofgumBconferred a severe loss of the secondary metabolites prodigiosin and serratamolide. ThegumBmutation conferred pleiotropic phenotypes, including altered biofilm formation, highly increased capsular polysaccharide production, and loss of swimming and swarming motility. These phenotypes corresponded to transcriptional changes infimA,wecA, andflhD. Unlike other UmoB/IgaA family members,gumBwas found to be not essential for growth inS. marcescens, yetigaAfromSalmonella enterica,yrfFfromEscherichia coli, and an uncharacterized predicted ortholog fromKlebsiella pneumoniaecomplemented thegumBmutant secondary metabolite defects, suggesting highly conserved function. These data support the idea that UmoB/IgaA family proteins are functionally conserved and extend the known regulatory influence of UmoB/IgaA family proteins to the control of competition-associated secondary metabolites and biofilm formation.IMPORTANCEIgaA/UmoB family proteins are found in members of theEnterobacteriaceaefamily of bacteria, which are of environmental and public health importance. IgaA/UmoB family proteins are thought to be inner membrane proteins that report extracellular stresses to intracellular signaling pathways that respond to environmental challenge. This study introduces a new member of the IgaA/UmoB family and demonstrates a high degree of functional similarity between IgaA/UmoB family proteins. Moreover, this study extends the phenomena controlled by IgaA/UmoB family proteins to include the biosynthesis of antimicrobial secondary metabolites.

scholarly journals Response of Secondary Metabolism of Hypogean Actinobacterial Genera to Chemical and Biological Stimuli

2018 ◽  
Vol 84 (19) ◽  
Author(s):  
Brett C. Covington ◽  
Jeffrey M. Spraggins ◽  
Audrey E. Ynigez-Gutierrez ◽  
Zachary B. Hylton ◽  
Brian O. Bachmann
Keyword(s):  
Secondary Metabolites ◽  
Small Molecules ◽  
Mixed Culture ◽  
Secondary Metabolite ◽  
Biologically Active ◽  
Secondary Metabolite Production ◽  
Microbial Culture ◽  
Content Type ◽  
Metabolite Production ◽  
Comparative Metabolomics

ABSTRACT Microorganisms within microbial communities respond to environmental challenges by producing biologically active secondary metabolites, yet the majority of these small molecules remain unidentified. We have previously demonstrated that secondary metabolite biosynthesis in actinomycetes can be activated by model environmental chemical and biological stimuli, and metabolites can be identified by comparative metabolomics analyses under different stimulus conditions. Here, we surveyed the secondary metabolite productivity of a group of 20 phylogenetically diverse actinobacteria isolated from hypogean (cave) environments by applying a battery of stimuli consisting of exposure to antibiotics, metals, and mixed microbial culture. Comparative metabolomics was used to reveal secondary metabolite responses from stimuli. These analyses revealed substantial changes in global metabolomic dynamics, with over 30% of metabolomic features increasing more than 10-fold under at least one stimulus condition. Selected features were isolated and identified via nuclear magnetic resonance (NMR), revealing several known secondary metabolite families, including the tetarimycins, aloesaponarins, hypogeamicins, actinomycins, and propeptins. One prioritized metabolite was identified to be a previously unreported aminopolyol polyketide, funisamine, produced by a cave isolate of Streptosporangium when exposed to mixed culture. The production of funisamine was most significantly increased in mixed culture with Bacillus species. The biosynthetic gene cluster responsible for the production of funisamine was identified via genomic sequencing of the producing strain, Streptosporangium sp. strain KDCAGE35, which facilitated a deduction of its biosynthesis. Together, these data demonstrate that comparative metabolomics can reveal the stimulus-induced production of natural products from diverse microbial phylogenies. IMPORTANCE Microbial secondary metabolites are an important source of biologically active and therapeutically relevant small molecules. However, much of this active molecular diversity is challenging to access due to low production levels or difficulty in discerning secondary metabolites within complex microbial extracts prior to isolation. Here, we demonstrate that ecological stimuli increase secondary metabolite production in phylogenetically diverse actinobacteria isolated from understudied hypogean environments. Additionally, we show that comparative metabolomics linking stimuli to metabolite response data can effectively reveal secondary metabolites within complex biological extracts. This approach highlighted secondary metabolites in almost all observed natural product classes, including low-abundance analogs of biologically relevant metabolites, as well as a new linear aminopolyol polyketide, funisamine. This study demonstrates the generality of activating stimuli to potentiate secondary metabolite production across diverse actinobacterial genera.

scholarly journals Serratia marcescens Quinoprotein Glucose Dehydrogenase Activity Mediates Medium Acidification and Inhibition of Prodigiosin Production by Glucose

2012 ◽  
Vol 78 (17) ◽  
pp. 6225-6235 ◽  
Author(s):  
James E. Fender ◽  
Cody M. Bender ◽  
Nicholas A. Stella ◽  
Roni M. Lahr ◽  
Eric J. Kalivoda ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Serratia Marcescens ◽  
Large Scale ◽  
Transcriptional Control ◽  
Glucose Dehydrogenase ◽  
Model Organism ◽  
Inhibitory Effect ◽  
Biologically Active ◽  
Scale Production ◽  
Content Type

ABSTRACTSerratia marcescensis a model organism for the study of secondary metabolites. The biologically active pigment prodigiosin (2-methyl-3-pentyl-6-methoxyprodiginine), like many other secondary metabolites, is inhibited by growth in glucose-rich medium. Whereas previous studies indicated that this inhibitory effect was pH dependent and did not require cyclic AMP (cAMP), there is no information on the genes involved in mediating this phenomenon. Here we used transposon mutagenesis to identify genes involved in the inhibition of prodigiosin by glucose. Multiple genetic loci involved in quinoprotein glucose dehydrogenase (GDH) activity were found to be required for glucose inhibition of prodigiosin production, including pyrroloquinoline quinone and ubiquinone biosynthetic genes. Upon assessing whether the enzymatic products of GDH activity were involved in the inhibitory effect, we observed thatd-glucono-1,5-lactone andd-gluconic acid, but notd-gluconate, were able to inhibit prodigiosin production. These data support a model in which the oxidation ofd-glucose by quinoprotein GDH initiates a reduction in pH that inhibits prodigiosin production through transcriptional control of the prodigiosin biosynthetic operon, providing new insight into the genetic pathways that control prodigiosin production. Strains generated in this report may be useful in large-scale production of secondary metabolites.

scholarly journals A Two-Step Mechanism for the Activation of Actinorhodin Export and Resistance in Streptomyces coelicolor

mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Ye Xu ◽  
Andrew Willems ◽  
Catherine Au-yeung ◽  
Kapil Tahlan ◽  
Justin R. Nodwell
Keyword(s):  
Secondary Metabolites ◽  
Pathogenic Bacteria ◽  
Streptomyces Coelicolor ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Resistance Mechanisms ◽  
Biosynthetic Gene ◽  
Content Type

ABSTRACT Many microorganisms produce secondary metabolites that have antibiotic activity. To avoid self-inhibition, the producing cells often encode cognate export and/or resistance mechanisms in the biosynthetic gene clusters for these molecules. Actinorhodin is a blue-pigmented antibiotic produced by Streptomyces coelicolor. The actAB operon, carried in the actinorhodin biosynthetic gene cluster, encodes two putative export pumps and is regulated by the transcriptional repressor protein ActR. In this work, we show that normal actinorhodin yields require actAB expression. Consistent with previous in vitro work, we show that both actinorhodin and its 3-ring biosynthetic intermediates [e.g., (S)-DNPA] can relieve repression of actAB by ActR in vivo. Importantly, an ActR mutant that interacts productively with (S)-DNPA but not with actinorhodin responds to the actinorhodin biosynthetic pathway with the induction of actAB and normal yields of actinorhodin. This suggests that the intermediates are sufficient to trigger the export genes in actinorhodin-producing cells. We further show that actinorhodin-producing cells can induce actAB expression in nonproducing cells; however, in this case actinorhodin is the most important signal. Finally, while the “intermediate-only” ActR mutant permits sufficient actAB expression for normal actinorhodin yields, this expression is short-lived. Sustained culture-wide expression requires a subsequent actinorhodin-mediated signaling step, and the defect in this response causes widespread cell death. These results are consistent with a two-step model for actinorhodin export and resistance where intermediates trigger initial expression for export from producing cells and actinorhodin then triggers sustained export gene expression that confers culture-wide resistance. IMPORTANCE Understanding the links between antibiotic resistance and biosynthesis is important for our efforts to manipulate secondary metabolism. For example, many secondary metabolites are produced at low levels; our work suggests that manipulating export might be one way to enhance yields of these molecules. It also suggests that understanding resistance will be relevant to the generation of novel secondary metabolites through the creation of synthetic secondary metabolic gene clusters. Finally, these cognate resistance mechanisms are related to mechanisms that arise in pathogenic bacteria, and understanding them is relevant to our ability to control microbial infections clinically.

scholarly journals Artificial Chromosomes to Explore and to Exploit Biosynthetic Capabilities of Actinomycetes

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Rosa Alduina ◽  
Giuseppe Gallo
Keyword(s):  
Secondary Metabolites ◽  
Antitumor Agents ◽  
Genetic Manipulation ◽  
Gene Clusters ◽  
Complex Compounds ◽  
Biologically Active ◽  
Biosynthetic Gene Clusters ◽  
Artificial Chromosomes ◽  
Pharmacokinetic Properties ◽  
New Strategies

Actinomycetes are an important source of biologically active compounds, like antibiotics, antitumor agents, and immunosuppressors. Genome sequencing is revealing that this class of microorganisms has larger genomes relative to other bacteria and uses a considerable fraction of its coding capacity (5–10%) for the production of mostly cryptic secondary metabolites. To access actinomycetes biosynthetic capabilities or to improve the pharmacokinetic properties and production yields of these chemically complex compounds, genetic manipulation of the producer strains can be performed. Heterologous expression in amenable hosts can be useful to exploit and to explore the genetic potential of actinomycetes and not cultivable but interesting bacteria. Artificial chromosomes that can be stably integrated into theStreptomycesgenome were constructed and demonstrated to be effective for transferring entire biosynthetic gene clusters from intractable actinomycetes into more suitable hosts. In this paper, the construction of several shuttleEscherichia coli-Streptomycesartificial chromosomes is discussed together with old and new strategies applied to improve heterologous production of secondary metabolites.

scholarly journals Lincomycin at Subinhibitory Concentrations Potentiates Secondary Metabolite Production by Streptomyces spp.

2015 ◽  
Vol 81 (11) ◽  
pp. 3869-3879 ◽  
Author(s):  
Yu Imai ◽  
Seizo Sato ◽  
Yukinori Tanaka ◽  
Kozo Ochi ◽  
Takeshi Hosaka
Keyword(s):  
Secondary Metabolites ◽  
Streptomyces Coelicolor ◽  
Regulatory Gene ◽  
Biosynthetic Gene Cluster ◽  
Mass Spectrometry Analysis ◽  
Antibacterial Compounds ◽  
Content Type ◽  
Spectrometry Analysis ◽  
Streptomyces Spp ◽  
Subinhibitory Concentrations

ABSTRACTAntibiotics have either bactericidal or bacteriostatic activity. However, they also induce considerable gene expression in bacteria when used at subinhibitory concentrations (below the MIC). We found that lincomycin, which inhibits protein synthesis by binding to the ribosomes of Gram-positive bacteria, was effective for inducing the expression of genes involved in secondary metabolism inStreptomycesstrains when added to medium at subinhibitory concentrations. InStreptomyces coelicolorA3(2), lincomycin at 1/10 of its MIC markedly increased the expression of the pathway-specific regulatory geneactII-ORF4 in the blue-pigmented antibiotic actinorhodin (ACT) biosynthetic gene cluster, which resulted in ACT overproduction. Intriguingly,S. lividans1326 grown in the presence of lincomycin at a subinhibitory concentration (1/12 or 1/3 of its MIC) produced abundant antibacterial compounds that were not detected in cells grown in lincomycin-free medium. Bioassay and mass spectrometry analysis revealed that some antibacterial compounds were novel congeners of calcium-dependent antibiotics. Our results indicate that lincomycin at subinhibitory concentrations potentiates the production of secondary metabolites inStreptomycesstrains and suggest that activating these strains by utilizing the dose-response effects of lincomycin could be used to effectively induce the production of cryptic secondary metabolites. In addition to these findings, we also report that lincomycin used at concentrations for markedly increased ACT production resulted in alteration of the cytoplasmic protein (FoF1ATP synthase α and β subunits, etc.) profile and increased intracellular ATP levels. A fundamental mechanism for these unique phenomena is also discussed.

scholarly journals Marine Actinomycetes, New Sources of Biotechnological Products

Marine Drugs ◽  
2021 ◽  
Vol 19 (7) ◽  
pp. 365
Author(s):  
Sveta V. Jagannathan ◽  
Erika M. Manemann ◽  
Sarah E. Rowe ◽  
Maiya C. Callender ◽  
William Soto
Keyword(s):  
Secondary Metabolites ◽  
Pathogenic Bacteria ◽  
Applied Research ◽  
Antitumor Agents ◽  
Current Knowledge ◽  
Industrial Applications ◽  
Future Research ◽  
Marine Actinomycetes ◽  
Food Preservatives ◽  
New Compounds

The Actinomycetales order is one of great genetic and functional diversity, including diversity in the production of secondary metabolites which have uses in medical, environmental rehabilitation, and industrial applications. Secondary metabolites produced by actinomycete species are an abundant source of antibiotics, antitumor agents, anthelmintics, and antifungals. These actinomycete-derived medicines are in circulation as current treatments, but actinomycetes are also being explored as potential sources of new compounds to combat multidrug resistance in pathogenic bacteria. Actinomycetes as a potential to solve environmental concerns is another area of recent investigation, particularly their utility in the bioremediation of pesticides, toxic metals, radioactive wastes, and biofouling. Other applications include biofuels, detergents, and food preservatives/additives. Exploring other unique properties of actinomycetes will allow for a deeper understanding of this interesting taxonomic group. Combined with genetic engineering, microbial experimental evolution, and other enhancement techniques, it is reasonable to assume that the use of marine actinomycetes will continue to increase. Novel products will begin to be developed for diverse applied research purposes, including zymology and enology. This paper outlines the current knowledge of actinomycete usage in applied research, focusing on marine isolates and providing direction for future research.

scholarly journals Serratia marcescens Cyclic AMP Receptor Protein Controls Transcription of EepR, a Novel Regulator of Antimicrobial Secondary Metabolites

2015 ◽  
Vol 197 (15) ◽  
pp. 2468-2478 ◽  
Author(s):  
Nicholas A. Stella ◽  
Roni M. Lahr ◽  
Kimberly M. Brothers ◽  
Eric J. Kalivoda ◽  
Kristin M. Hunt ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Secondary Metabolites ◽  
Cyclic Amp ◽  
Serratia Marcescens ◽  
Therapeutic Potential ◽  
Response Regulator ◽  
Biologically Active ◽  
Receptor Protein ◽  
Content Type

ABSTRACTSerratia marcescensgenerates secondary metabolites and secreted enzymes, and it causes hospital infections and community-acquired ocular infections. Previous studies identified cyclic AMP (cAMP) receptor protein (CRP) as an indirect inhibitor of antimicrobial secondary metabolites. Here, we identified a putative two-component regulator that suppressedcrpmutant phenotypes. Evidence supports that the putative response regulatoreepRwas directly transcriptionally inhibited by cAMP-CRP. EepR and the putative sensor kinase EepS were necessary for the biosynthesis of secondary metabolites, including prodigiosin- and serratamolide-dependent phenotypes, swarming motility, and hemolysis. Recombinant EepR bound to the prodigiosin and serratamolide promotersin vitro. Together, these data introduce a novel regulator of secondary metabolites that directly connects the broadly conserved metabolism regulator CRP with biosynthetic genes that may contribute to competition with other microbes.IMPORTANCEThis study identifies a new transcription factor that is directly controlled by a broadly conserved transcription factor, CRP. CRP is well studied in its role to help bacteria respond to the amount of nutrients in their environment. The new transcription factor EepR is essential for the bacteriumSerratia marcescensto produce two biologically active compounds, prodigiosin and serratamolide. These two compounds are antimicrobial and may allowS. marcescensto compete for limited nutrients with other microorganisms. Results from this study tie together the CRP environmental nutrient sensor with a new regulator of antimicrobial compounds. Beyond microbial ecology, prodigiosin and serratamolide have therapeutic potential; therefore, understanding their regulation is important for both applied and basic science.

scholarly journals MoLAEA Regulates Secondary Metabolism in Magnaporthe oryzae

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Pallabi Saha ◽  
Suvranil Ghosh ◽  
Subhankar Roy-Barman
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Filamentous Fungi ◽  
Magnaporthe Oryzae ◽  
Antitumor Agents ◽  
Negative Regulator ◽  
Blast Disease ◽  
Penicillin G ◽  
Content Type ◽  
First Time

ABSTRACT Fungi are rich sources of secondary metabolites of pharmaceutical importance, such as antibiotics, antitumor agents, and immunosuppressants, as well as of harmful toxins. Secondary metabolites play important roles in the development and pathogenesis of fungi. LaeA is a global regulator of secondary metabolism and was originally reported in Aspergillus nidulans; however, its role in secondary metabolism in Magnaporthe oryzae has not yet been reported. Here, we investigated the role of a gene homologous to LAEA (loss of AflR expression) of Aspergillus spp. in Magnaporthe oryzae, named M. oryzae LAEA (MoLAEA). Studies on MoLAEA overexpression and knockdown strains have suggested that this gene acts as a negative regulator of sporulation and melanin synthesis. However, it is not involved in the growth and pathogenesis of M. oryzae. Transcriptomic data indicated that MoLAEA regulated genes involved in secondary metabolism. Interestingly, we observed (for the first time, to our knowledge) that this gene is involved in benzylpenicillin (penicillin G) synthesis in M. oryzae. Overexpression of MoLAEA increased penicillin G production, whereas the silenced strain showed a complete absence of penicillin G compared to its presence in the wild type. We also observed that MoLaeA interacted with MoVeA, a velvet family protein involved in fungal development and secondary metabolism, in the nucleus. This study showed that though MoLAEA may not make any contribution in rice blast fungal pathogenesis, it regulates secondary metabolism in M. oryzae and thus can be further studied for identifying other new uncharacterized metabolites in this fungus. IMPORTANCE M. oryzae causes blast disease, the most serious disease of cultivated rice affecting global rice production. The genome of M. oryzae has been shown to have a number of genes involved in secondary metabolism, but most of them are uncharacterized. In fact, compared to studies of other filamentous fungi, hardly any work has been done on secondary metabolism in M. oryzae. It is shown here (for the first time, to our knowledge) that penicillin G is being synthesized in M. oryzae and that MoLAEA is involved in this process. This is the first step in understanding the penicillin G biosynthesis pathway in M. oryzae. This study also unraveled the details of how MoLaeA works by forming a nuclear complex with MoVeA in M. oryzae, thus indicating functional conservation of such a gene across filamentous fungi. All these findings open up avenues for more relevant investigations on the genetic regulation of secondary metabolism in M. oryzae.

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