Targeted production of secondary metabolites by coexpression of non-ribosomal peptide synthetase and prenyltransferase genes in Aspergillus

2015 ◽  
Vol 99 (10) ◽  
pp. 4213-4223 ◽  
Author(s):  
Carsten Wunsch ◽  
Kathrin Mundt ◽  
Shu-Ming Li
Keyword(s):  
Secondary Metabolites ◽  
Peptide Synthetase

scholarly journals Terpenoid Biosynthesis Dominates among Secondary Metabolite Clusters in Mucoromycotina Genomes

2021 ◽  
Vol 7 (4) ◽  
pp. 285
Author(s):  
Grzegorz Koczyk ◽  
Julia Pawłowska ◽  
Anna Muszewska
Keyword(s):  
Secondary Metabolites ◽  
Growth Promotion ◽  
Iron Chelation ◽  
Biological Traits ◽  
Terpenoid Biosynthesis ◽  
Gene Model ◽  
Model Quality ◽  
The Core ◽  
Domain Composition ◽  
Peptide Synthetase

Early-diverging fungi harbour unprecedented diversity in terms of living forms, biological traits and genome architecture. Before the sequencing era, non-Dikarya fungi were considered unable to produce secondary metabolites (SM); however, this perspective is changing. The main classes of secondary metabolites in fungi include polyketides, nonribosomal peptides, terpenoids and siderophores that serve different biological roles, including iron chelation and plant growth promotion. The same classes of SM are reported for representatives of early-diverging fungal lineages. Encouraged by the advancement in the field, we carried out a systematic survey of SM in Mucoromycotina and corroborated the presence of various SM clusters (SMCs) within the phylum. Among the core findings, considerable representation of terpene and nonribosomal peptide synthetase (NRPS)-like candidate SMCs was found. Terpene clusters with diverse domain composition and potentially highly variable products dominated the landscape of candidate SMCs. A uniform low-copy distribution of siderophore clusters was observed among most assemblies. Mortierellomycotina are highlighted as the most potent SMC producers among the Mucoromycota and as a source of novel peptide products. SMC identification is dependent on gene model quality and can be successfully performed on a batch scale with genomes of different quality and completeness.

scholarly journals The Draft Genome Sequence of The Endophytic Streptomyces Strain VITGV156

2021 ◽  
Author(s):  
Veilumuthu P ◽  
Nagarajan T ◽  
Sasikumar S ◽  
Siva R ◽  
J Godwin Christopher
Keyword(s):  
Secondary Metabolites ◽  
Draft Genome ◽  
Gc Content ◽  
Gene Clusters ◽  
Dominant Group ◽  
Protein Coding ◽  
Peptide Synthetase ◽  
The Family ◽  
Modified Peptides ◽  
Endophytic Streptomyces

Abstract Streptomyces species is one among the dominant group of bacteria in the family Actinobacteria with a rich repertoire of secondary metabolites. Secondary metabolites with antimicrobial activity and plant growth promotor have been isolated from various Streptomyces sp. Here in this investigation, we present the draft genome of a new species, Streptomyces sp. VITGV156 isolated from healthy tomato plant (Lycopersicon esculentum) which has some rare antimicrobial secondary metabolites, like coelichelin, fluostatins, vicenistatin, nystatin, sipanmycin, and informatipeptin. The genome is 8.18 Mb in size with 6,259 protein coding genes. The average GC content of the genome is 72.61 %. Preliminary analysis with antiSMASH 6.0 revealed the presence of 29 biosynthetic gene clusters for the synthesis of potential secondary metabolites. These includes 4 NRPS (non – ribosomal peptide synthetase), 7 PKS (Polyketide Synthases), 2 RiPP (Ribosomally synthesized and post-translationally modified peptides) clusters. When we look into genes associated with secondary metabolites, 406 genes are present which includes 184 genes for cofactor and vitamins, 72 genes for terpenoids and polyketides, 70 genes for xenobiotics and 80 genes for other metabolites are present. Comparative genome analysis of VITGV156 with its closest neighbor Streptomyces luteus strain TRM45540 revealed ANI 91.22% and dDDH value 44.00%.

scholarly journals Polyketide Synthase and Nonribosomal Peptide Synthetase Gene Clusters in Type Strains of the Genus Phytohabitans

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 257
Author(s):  
Hisayuki Komaki ◽  
Tomohiko Tamura
Keyword(s):  
Secondary Metabolites ◽  
Polyketide Synthase ◽  
Gene Clusters ◽  
Nonribosomal Peptide Synthetase ◽  
Nrps Gene ◽  
Nonribosomal Peptide ◽  
Rare Actinomycetes ◽  
Whole Genomes ◽  
Peptide Synthetase ◽  
Established Genus

(1) Background: Phytohabitans is a recently established genus belonging to rare actinomycetes. It has been unclear if its members have the capacity to synthesize diverse secondary metabolites. Polyketide and nonribosomal peptide compounds are major secondary metabolites in actinomycetes and expected as a potential source for novel pharmaceuticals. (2) Methods: Whole genomes of Phytohabitans flavus NBRC 107702T, Phytohabitans rumicis NBRC 108638T, Phytohabitans houttuyneae NBRC 108639T, and Phytohabitans suffuscus NBRC 105367T were sequenced by PacBio. Polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) gene clusters were bioinformatically analyzed in the genome sequences. (3) Results: These four strains harbored 10, 14, 18 and 14 PKS and NRPS gene clusters, respectively. Most of the gene clusters were annotated to synthesis unknown chemistries. (4) Conclusions: Members of the genus Phytohabitans are a possible source for novel and diverse polyketides and nonribosomal peptides.

scholarly journals Moorea producens gen. nov., sp. nov. and Moorea bouillonii comb. nov., tropical marine cyanobacteria rich in bioactive secondary metabolites

2012 ◽  
Vol 62 (Pt_5) ◽  
pp. 1171-1178 ◽  
Author(s):  
Niclas Engene ◽  
Erin C. Rottacker ◽  
Jan Kaštovský ◽  
Tara Byrum ◽  
Hyukjae Choi ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Polyketide Synthase ◽  
Botanical Nomenclature ◽  
Distinctive Character ◽  
Content Type ◽  
Algae Blooms ◽  
Rich Diversity ◽  
Peptide Synthetase ◽  
Bioactive Secondary Metabolites ◽  
Micro Organisms

The filamentous cyanobacterial genus Moorea gen. nov., described here under the provisions of the International Code of Botanical Nomenclature, is a cosmopolitan pan-tropical group abundant in the marine benthos. Members of the genus Moorea are photosynthetic (containing phycocyanin, phycoerythrin, allophycocyanin and chlorophyll a), but non-diazotrophic (lack heterocysts and nitrogenase reductase genes). The cells (discoid and 25–80 µm wide) are arranged in long filaments (<10 cm in length) and often form extensive mats or blooms in shallow water. The cells are surrounded by thick polysaccharide sheaths covered by a rich diversity of heterotrophic micro-organisms. A distinctive character of this genus is its extraordinarily rich production of bioactive secondary metabolites. This is matched by genomes rich in polyketide synthase and non-ribosomal peptide synthetase biosynthetic genes which are dedicated to secondary metabolism. The encoded natural products are sometimes responsible for harmful algae blooms and, due to morphological resemblance to the genus Lyngbya , this group has often been incorrectly cited in the literature. We here describe two species of the genus Moorea: Moorea producens sp. nov. (type species of the genus) with 3LT as the nomenclature type, and Moorea bouillonii comb. nov. with PNG5-198R as the nomenclature type.

scholarly journals Integrated omics unveil the secondary metabolic landscape of a basal dinoflagellate

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Girish Beedessee ◽  
Takaaki Kubota ◽  
Asuka Arimoto ◽  
Koki Nishitsuji ◽  
Ross F. Waller ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Harmful Algal Blooms ◽  
Algal Blooms ◽  
Toxin Production ◽  
Mrna Isoforms ◽  
Peptide Synthetase ◽  
Integrated Omics ◽  
Large Genome Size ◽  
Post Transcriptional Regulation ◽  
First Time

Abstract Background Some dinoflagellates cause harmful algal blooms, releasing toxic secondary metabolites, to the detriment of marine ecosystems and human health. Our understanding of dinoflagellate toxin biosynthesis has been hampered by their unusually large genomes. To overcome this challenge, for the first time, we sequenced the genome, microRNAs, and mRNA isoforms of a basal dinoflagellate, Amphidinium gibbosum, and employed an integrated omics approach to understand its secondary metabolite biosynthesis. Results We assembled the ~ 6.4-Gb A. gibbosum genome, and by probing decoded dinoflagellate genomes and transcriptomes, we identified the non-ribosomal peptide synthetase adenylation domain as essential for generation of specialized metabolites. Upon starving the cells of phosphate and nitrogen, we observed pronounced shifts in metabolite biosynthesis, suggestive of post-transcriptional regulation by microRNAs. Using Iso-Seq and RNA-seq data, we found that alternative splicing and polycistronic expression generate different transcripts for secondary metabolism. Conclusions Our genomic findings suggest intricate integration of various metabolic enzymes that function iteratively to synthesize metabolites, providing mechanistic insights into how dinoflagellates synthesize secondary metabolites, depending upon nutrient availability. This study provides insights into toxin production associated with dinoflagellate blooms. The genome of this basal dinoflagellate provides important clues about dinoflagellate evolution and overcomes the large genome size, which has been a challenge previously.

scholarly journals Activation of cryptic metabolite production through gene disruption: Dimethyl furan-2,4-dicarboxylate produced by Streptomyces sahachiroi

2013 ◽  
Vol 9 ◽  
pp. 1768-1773 ◽  
Author(s):  
Dinesh Simkhada ◽  
Huitu Zhang ◽  
Shogo Mori ◽  
Howard Williams ◽  
Coran M H Watanabe
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Small Molecule ◽  
Related Compound ◽  
Gene Disruption ◽  
Genome Sequences ◽  
Bioactive Natural Products ◽  
Genetic Knockout ◽  
Small Molecule Drugs ◽  
Peptide Synthetase

At least 65% of all small molecule drugs on the market today are natural products, however, re-isolation of previously identified and characterized compounds has become a serious impediment to the discovery of new bioactive natural products. Here, genetic knockout of an unusual non-ribosomal peptide synthetase (NRPS) C-PCP-C module, aziA2, is performed resulting in the accumulation of the secondary metabolite, dimethyl furan-2,4-dicarboxylate. The cryptic metabolite represents the first non-azinomycin related compound to be isolated and characterized from the soil bacterium, S. sahachiroi. The results from this study suggest that abolishing production of otherwise predominant natural products through genetic knockout may constitute a means to “activate” the production of novel secondary metabolites that would otherwise lay dormant within microbial genome sequences.

scholarly journals Bioactivity and genetic screening of marine actinobacteria associated with red algae Gelidiella acerosa

2018 ◽  
Vol 22 (1) ◽  
pp. 13 ◽  
Author(s):  
Maria Ulfah ◽  
Noer Kasanah ◽  
Niken Satiti Nur Handayani
Keyword(s):  
Secondary Metabolites ◽  
Red Algae ◽  
Genetic Screening ◽  
Bacterial Resistance ◽  
Marine Actinobacteria ◽  
Gelidiella Acerosa ◽  
Peptide Synthetase ◽  
New Antibiotics ◽  
Mini Plate ◽  
Microtiter Assay

Bacterial resistance to existing antibiotics has driven a search for new antibiotics from marine actinobacteria. Bioactivity and genetic screening of actinobacteria associated with red algae Gelidiella acerosa were conducted to discover new antibacterial compounds against Vibrio alginolyticus. A total of 14 actinobacteria isolates were obtained from G. acerosa. The isolates were subjected to genetic screening for nrps (non-ribosomal peptide synthetase) and FADH2-dependent halogenase genes. The isolates’ ability to produce secondary metabolites was examined by fermentation in various media in a six-well mini plate. The bioactivity of the secondary metabolites was screened using a microtiter assay and the agar overlay method. The results showed that all 14 isolates had the nrps gene, whereas none had the halogenase gene. Meanwhile, eight of the actinobacteria isolates showed antibacterial activity against V. alginolyticus.

scholarly journals Diversity of Bacterial Biosynthetic Genes in Maritime Antarctica

2020 ◽  
Vol 8 (2) ◽  
pp. 279 ◽  
Author(s):  
Adriana Rego ◽  
António G. G. Sousa ◽  
João P. Santos ◽  
Francisco Pascoal ◽  
João Canário ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Polyketide Synthase ◽  
Amplicon Sequencing ◽  
Soil Samples ◽  
Chemical Diversity ◽  
Maritime Antarctica ◽  
Biosynthetic Genes ◽  
Peptide Synthetase ◽  
Drug Leads ◽  
Culture Dependent

Bacterial natural products (NPs) are still a major source of new drug leads. Polyketides (PKs) and non-ribosomal peptides (NRP) are two pharmaceutically important families of NPs and recent studies have revealed Antarctica to harbor endemic polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes, likely to be involved in the production of novel metabolites. Despite this, the diversity of secondary metabolites genes in Antarctica is still poorly explored. In this study, a computational bioprospection approach was employed to study the diversity and identity of PKS and NRPS genes to one of the most biodiverse areas in maritime Antarctica—Maxwell Bay. Amplicon sequencing of soil samples targeting ketosynthase (KS) and adenylation (AD) domains of PKS and NRPS genes, respectively, revealed abundant and unexplored chemical diversity in this peninsula. About 20% of AD domain sequences were only distantly related to characterized biosynthetic genes. Several PKS and NRPS genes were found to be closely associated to recently described metabolites including those from uncultured and candidate phyla. The combination of new approaches in computational biology and new culture-dependent and -independent strategies is thus critical for the recovery of the potential novel chemistry encoded in Antarctica microorganisms.

scholarly journals Dickeya solani D s0432-1 produces an arsenal of secondary metabolites with anti-prokaryotic and anti-eukaryotic activities against bacteria, yeasts, fungi, and aphids.

2021 ◽  
Author(s):  
G&eacuteraldine Effantin ◽  
Typhaine Brual ◽  
Yvan Rahb&eacute ◽  
Nicole Hugouvieux-Cotte-Pattat ◽  
Erwan Gueguen
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Reverse Genetics ◽  
Gram Negative Bacteria ◽  
Plant Pathogenic Bacterium ◽  
Wide Range ◽  
Peptide Synthetase ◽  
Rapid Spread ◽  
Dickeya Solani ◽  
Growth Of Fungi

The necrotrophic plant pathogenic bacterium Dickeya solani is a new invader of potato agrosystem in Europe. All isolated strains of D. solani contain several large polyketide/fatty acid/non-ribosomal peptide synthetase clusters. Analogy with genes described in other bacteria, suggests that two clusters are involved in the production of secondary metabolites of the oocydin and zeamine family. In this study, we constructed by an approach of reverse genetics mutants affected in the three secondary metabolite clusters ssm, ooc and zms in order to compare the phenotype of the D. solani strain D s0432-1 with its derived mutants. We demonstrated that the zeamine cluster inhibits growth of gram-positive and gram-negative bacteria. It is also implicated in a toxicity against aphids. The oocydin cluster inhibits growth of fungi of the phylum Ascomycota. Finally, we unveiled the function of a new secondary metabolite cluster (ssm, for solani secondary metabolite), only conserved in some Dickeya species. This cluster produces a secondary metabolite inhibiting yeasts. D. solani therefore produces several molecules that are toxic to a wide range of living and potentially interacting organisms, from bacteria to insects. The expression of these secondary metabolite pathways could contribute to the rapid spread of D. solani in Europe.

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