scholarly journals A secondary metabolite drives intraspecies antagonism in a gut symbiont that is inhibited by peptidoglycan acetylation

2021 ◽  
Author(s):  
Mustafa Özçam ◽  
Jee-Hwan Oh ◽  
Restituto Tocmo ◽  
Deepa Acharya ◽  
Shenwei Zhang ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Polyketide Synthase ◽  
Gene Clusters ◽  
Polyketide Synthase Gene ◽  
Microbe Interactions ◽  
Host Origin ◽  
Gut Symbionts ◽  
Intraspecies Competition ◽  
Genome Analyses

The mammalian microbiome encodes numerous secondary metabolite biosynthetic gene clusters, yet their role in microbe-microbe interactions is unclear. Here, we characterized two polyketide synthase gene clusters (fun and pks) in the gut symbiont Limosilactobacillus reuteri. The pks, but not the fun cluster, encodes antimicrobial activity. Forty-one out of 51 L. reuteri strains tested are sensitive to Pks products, which was independent of strains host origin. The sensitivity to Pks was also established in intraspecies competition experiments in gnotobiotic mice. Comparative genome analyses between Pks-resistant and sensitive strains identified an acyltransferase gene (act) that is unique to Pks-resistant strains. Subsequent peptidoglycan analysis of the wild-type and the act mutant strains showed that Act acetylates peptidoglycan. The pks mutants lost their competitive advantage and act mutants lost their Pks resistance in vivo. Thus, our findings provide mechanistic insights into how closely related gut symbionts can compete and co-exist in the gastrointestinal tract.

scholarly journals The Fusarium verticillioides FUM Gene Cluster Encodes a Zn(II)2Cys6 Protein That Affects FUM Gene Expression and Fumonisin Production

2007 ◽  
Vol 6 (7) ◽  
pp. 1210-1218 ◽  
Author(s):  
Daren W. Brown ◽  
Robert A. E. Butchko ◽  
Mark Busman ◽  
Robert H. Proctor
Keyword(s):  
Gene Cluster ◽  
Polyketide Synthase ◽  
Fusarium Verticillioides ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Regulatory Proteins ◽  
Wild Type ◽  
Polyketide Synthase Gene ◽  
Splice Forms ◽  
Self Protection

ABSTRACT Fumonisins are mycotoxins produced by some Fusarium species and can contaminate maize or maize products. Ingestion of fumonisins is associated with diseases, including cancer and neural tube defects, in humans and animals. In fungi, genes involved in the synthesis of mycotoxins and other secondary metabolites are often located adjacent to each other in gene clusters. Such genes can encode structural enzymes, regulatory proteins, and/or proteins that provide self-protection. The fumonisin biosynthetic gene cluster includes 16 genes, none of which appear to play a role in regulation. In this study, we identified a previously undescribed gene (FUM21) located adjacent to the fumonisin polyketide synthase gene, FUM1. The presence of a Zn(II)2Cys6 DNA-binding domain in the predicted protein suggested that FUM21 was involved in transcriptional regulation. FUM21 deletion (Δfum21) mutants produce little to no fumonisin in cracked maize cultures but some FUM1 and FUM8 transcripts in a liquid GYAM medium. Complementation of a Δfum21 mutant with a wild-type copy of the gene restored fumonisin production. Analysis of FUM21 cDNAs identified four alternative splice forms (ASFs), and microarray analysis indicated the ASFs were differentially expressed. Based on these data, we present a model for how FUM21 ASFs may regulate fumonisin biosynthesis.

scholarly journals Genome-based survey of nonribosomal peptide synthetase and polyketide synthase gene clusters in type strains of the genus Microtetraspora

2016 ◽  
Vol 69 (9) ◽  
pp. 712-718 ◽  
Author(s):  
Hisayuki Komaki ◽  
Natsuko Ichikawa ◽  
Tomohiko Tamura ◽  
Akio Oguchi ◽  
Moriyuki Hamada ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Gene Clusters ◽  
Nonribosomal Peptide Synthetase ◽  
Nonribosomal Peptide ◽  
Peptide Synthetase ◽  
Polyketide Synthase Gene ◽  
Type Strains

scholarly journals Identification and Characterization of the Asperthecin Gene Cluster of Aspergillus nidulans

2008 ◽  
Vol 74 (24) ◽  
pp. 7607-7612 ◽  
Author(s):  
Edyta Szewczyk ◽  
Yi-Ming Chiang ◽  
C. Elizabeth Oakley ◽  
Ashley D. Davidson ◽  
Clay C. C. Wang ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Polyketide Synthase ◽  
Gene Clusters ◽  
Laboratory Culture ◽  
Culture Conditions ◽  
Type I ◽  
Genes Encoding ◽  
Identification And Characterization ◽  
Normal Laboratory

ABSTRACT The sequencing of Aspergillus genomes has revealed that the products of a large number of secondary metabolism pathways have not yet been identified. This is probably because many secondary metabolite gene clusters are not expressed under normal laboratory culture conditions. It is, therefore, important to discover conditions or regulatory factors that can induce the expression of these genes. We report that the deletion of sumO, the gene that encodes the small ubiquitin-like protein SUMO in A. nidulans, caused a dramatic increase in the production of the secondary metabolite asperthecin and a decrease in the synthesis of austinol/dehydroaustinol and sterigmatocystin. The overproduction of asperthecin in the sumO deletion mutant has allowed us, through a series of targeted deletions, to identify the genes required for asperthecin synthesis. The asperthecin biosynthesis genes are clustered and include genes encoding an iterative type I polyketide synthase, a hydrolase, and a monooxygenase. The identification of these genes allows us to propose a biosynthetic pathway for asperthecin.

scholarly journals Structural and Functional Characterization of Three Polyketide Synthase Gene Clusters in Bacillus amyloliquefaciens FZB 42

2006 ◽  
Vol 188 (11) ◽  
pp. 4024-4036 ◽  
Author(s):  
Xiao-Hua Chen ◽  
Joachim Vater ◽  
Jörn Piel ◽  
Peter Franke ◽  
Romy Scholz ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Bacillus Amyloliquefaciens ◽  
Polyketide Synthase ◽  
Functional Characterization ◽  
Gene Clusters ◽  
Ionization Mass ◽  
Bioactive Natural Products ◽  
Flight Mass Spectrometry ◽  
Polyketide Synthase Gene ◽  
Bacterial Sources

ABSTRACT Although bacterial polyketides are of considerable biomedical interest, the molecular biology of polyketide biosynthesis in Bacillus spp., one of the richest bacterial sources of bioactive natural products, remains largely unexplored. Here we assign for the first time complete polyketide synthase (PKS) gene clusters to Bacillus antibiotics. Three giant modular PKS systems of the trans-acyltransferase type were identified in Bacillus amyloliquefaciens FZB 42. One of them, pks1, is an ortholog of the pksX operon with a previously unknown function in the sequenced model strain Bacillus subtilis 168, while the pks2 and pks3 clusters are novel gene clusters. Cassette mutagenesis combined with advanced mass spectrometric techniques such as matrix-assisted laser desorption ionization-time of flight mass spectrometry and liquid chromatography-electrospray ionization mass spectrometry revealed that the pks1 (bae) and pks3 (dif) gene clusters encode the biosynthesis of the polyene antibiotics bacillaene and difficidin or oxydifficidin, respectively. In addition, B. subtilis OKB105 (pheA sfp 0), a transformant of the B. subtilis 168 derivative JH642, was shown to produce bacillaene, demonstrating that the pksX gene cluster directs the synthesis of that polyketide.

scholarly journals Breaking the Silence: Protein Stabilization Uncovers Silenced Biosynthetic Gene Clusters in the Fungus Aspergillus nidulans

2012 ◽  
Vol 78 (23) ◽  
pp. 8234-8244 ◽  
Author(s):  
Jennifer Gerke ◽  
Özgür Bayram ◽  
Kirstin Feussner ◽  
Manuel Landesfeind ◽  
Ekaterina Shelest ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Aspergillus Nidulans ◽  
Polyketide Synthase ◽  
Gene Clusters ◽  
Cellular Protein ◽  
Protein Stabilization ◽  
Putative Gene ◽  
Content Type ◽  
Alternative Approach ◽  
Polyketide Synthase Gene

ABSTRACTThe genomes of filamentous fungi comprise numerous putative gene clusters coding for the biosynthesis of chemically and structurally diverse secondary metabolites (SMs), which are rarely expressed under laboratory conditions. Previous approaches to activate these genes were based primarily on artificially targeting the cellular protein synthesis apparatus. Here, we applied an alternative approach of genetically impairing the protein degradation apparatus of the model fungusAspergillus nidulansby deleting the conserved eukaryoticcsnE/CSN5deneddylase subunit of the COP9 signalosome. This defect in protein degradation results in the activation of a previously silenced gene cluster comprising a polyketide synthase gene producing the antibiotic 2,4-dihydroxy-3-methyl-6-(2-oxopropyl)benzaldehyde (DHMBA). ThecsnE/CSN5gene is highly conserved in fungi, and therefore, the deletion is a feasible approach for the identification of new SMs.

scholarly journals Increased abundance of secreted hydrolytic enzymes and secondary metabolite gene clusters define the genomes of latent plant pathogens in the Botryosphaeriaceae

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jan H. Nagel ◽  
Michael J. Wingfield ◽  
Bernard Slippers
Keyword(s):  
Secondary Metabolite ◽  
Plant Pathogens ◽  
Plant Cell Wall ◽  
Hydrolytic Enzymes ◽  
Gene Clusters ◽  
Comparative Genomic ◽  
Biosynthetic Gene ◽  
Plant Interactions ◽  
Biosynthetic Gene Clusters ◽  
Genome Analyses

Abstract Background The Botryosphaeriaceae are important plant pathogens, but also have the ability to establish asymptomatic infections that persist for extended periods in a latent state. In this study, we used comparative genome analyses to shed light on the genetic basis of the interactions of these fungi with their plant hosts. For this purpose, we characterised secreted hydrolytic enzymes, secondary metabolite biosynthetic gene clusters and general trends in genomic architecture using all available Botryosphaeriaceae genomes, and selected Dothideomycetes genomes. Results The Botryosphaeriaceae genomes were rich in carbohydrate-active enzymes (CAZymes), proteases, lipases and secondary metabolic biosynthetic gene clusters (BGCs) compared to other Dothideomycete genomes. The genomes of Botryosphaeria, Macrophomina, Lasiodiplodia and Neofusicoccum, in particular, had gene expansions of the major constituents of the secretome, notably CAZymes involved in plant cell wall degradation. The Botryosphaeriaceae genomes were shown to have moderate to high GC contents and most had low levels of repetitive DNA. The genomes were not compartmentalized based on gene and repeat densities, but genes of secreted enzymes were slightly more abundant in gene-sparse regions. Conclusion The abundance of secreted hydrolytic enzymes and secondary metabolite BGCs in the genomes of Botryosphaeria, Macrophomina, Lasiodiplodia, and Neofusicoccum were similar to those in necrotrophic plant pathogens and some endophytes of woody plants. The results provide a foundation for comparative genomic analyses and hypotheses to explore the mechanisms underlying Botryosphaeriaceae host-plant interactions.

scholarly journals Potential secondary metabolite biosynthetic gene clusters and antibacterial activity of novel taxa Gandjariella

2020 ◽  
Vol 21 (12) ◽  
Author(s):  
Fitria Ningsih ◽  
Dhian Chitra Ayu Fitria Sari ◽  
Shuhei Yabe ◽  
Akira Yokota ◽  
Wellyzar Sjamsuridzal
Keyword(s):  
Antibacterial Activity ◽  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Polyketide Synthase ◽  
Gene Clusters ◽  
Gellan Gum ◽  
Biosynthetic Gene ◽  
Bacterial Strains ◽  
Biosynthetic Gene Clusters ◽  
Novel Taxa

Abstract. Ningsih F, Sari DCAF, Yabe S, Yokota A, Sjamsuridzal W. 2020. Potential secondary metabolite biosynthetic gene clusters and antibacterial activity of novel taxa Gandjariella. Biodiversitas 21: 5674-5684. Microbial resistance to available antibiotics has gained increasing attention in recent years and led to the urgent search for active secondary metabolites from novel microbial taxa. This study aimed to assess putative secondary metabolite biosynthetic gene clusters (BGCs) in the genome of a novel thermophilic Actinobacteria type strain Gandjariella thermophila SL3-2-4T and screen for its antibacterial activity. Four other related novel candidate Actinobacteria strains, isolated from forest soil in the Cisolok geothermal area (West Java, Indonesia), were also screened for antibacterial activity in various media solidified with gellan gum. The genome of the SL3-2-4T strain contained 21 antiSMASH-identified secondary metabolite regions harboring BGCs. These BGCs were for polyketide synthase, non-ribosomal peptide synthase, and ribosomally synthesized and post-translationally modified peptide family clusters. Three BGC regions displayed 50-100% similarity with known secondary metabolites. Thirteen and five regions displayed low (4-35%) and no similarity with known BGCs for secondary metabolites, respectively. Strains SL3-2-4T and SL3-2-7 on MM 2 medium solidified with gellan gum at 45 °C for 14 days demonstrated inhibitory activity against all Gram-positive, but not Gram-negative bacteria. Strain SL3-2-10 on ISP 3 gellan gum medium incubated for seven days only active against K. rhizophila NBRC 12078. Strains SL3-2-6 and SL3-2-9 did not exhibit any antibacterial activity against the tested bacterial strains on the three tested media. The results indicated that novel taxa have the potential for the discovery of active secondary metabolites.

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