scholarly journals Sequence-based classification of type II polyketide synthase biosynthetic gene clusters for antiSMASH

2019 ◽  
Vol 46 (3-4) ◽  
pp. 469-475 ◽  
Author(s):  
Rasmus Villebro ◽  
Simon Shaw ◽  
Kai Blin ◽  
Tilmann Weber
BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Hye-Seon Kim ◽  
Jessica M. Lohmar ◽  
Mark Busman ◽  
Daren W. Brown ◽  
Todd A. Naumann ◽  
...  

Abstract Background Sphingolipids are structural components and signaling molecules in eukaryotic membranes, and many organisms produce compounds that inhibit sphingolipid metabolism. Some of the inhibitors are structurally similar to the sphingolipid biosynthetic intermediate sphinganine and are referred to as sphinganine-analog metabolites (SAMs). The mycotoxins fumonisins, which are frequent contaminants in maize, are one family of SAMs. Due to food and feed safety concerns, fumonisin biosynthesis has been investigated extensively, including characterization of the fumonisin biosynthetic gene cluster in the agriculturally important fungi Aspergillus and Fusarium. Production of several other SAMs has also been reported in fungi, but there is almost no information on their biosynthesis. There is also little information on how widely SAM production occurs in fungi or on the extent of structural variation of fungal SAMs. Results Using fumonisin biosynthesis as a model, we predicted that SAM biosynthetic gene clusters in fungi should include a polyketide synthase (PKS), an aminotransferase and a dehydrogenase gene. Surveys of genome sequences identified five putative clusters with this three-gene combination in 92 of 186 Fusarium species examined. Collectively, the putative SAM clusters were distributed widely but discontinuously among the species. We propose that the SAM5 cluster confers production of a previously reported Fusarium SAM, 2-amino-14,16-dimethyloctadecan-3-ol (AOD), based on the occurrence of AOD production only in species with the cluster and on deletion analysis of the SAM5 cluster PKS gene. We also identified SAM clusters in 24 species of other fungal genera, and propose that one of the clusters confers production of sphingofungin, a previously reported Aspergillus SAM. Conclusion Our results provide a genomics approach to identify novel SAM biosynthetic gene clusters in fungi, which should in turn contribute to identification of novel SAMs with applications in medicine and other fields. Information about novel SAMs could also provide insights into the role of SAMs in the ecology of fungi. Such insights have potential to contribute to strategies to reduce fumonisin contamination in crops and to control crop diseases caused by SAM-producing fungi.


PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0121505 ◽  
Author(s):  
Yasushi Ogasawara ◽  
Benjamin J. Yackley ◽  
Jacob A. Greenberg ◽  
Snezna Rogelj ◽  
Charles E. Melançon

2018 ◽  
Vol 115 (15) ◽  
pp. 3758-3763 ◽  
Author(s):  
Johannes Arp ◽  
Sebastian Götze ◽  
Ruchira Mukherji ◽  
Derek J. Mattern ◽  
María García-Altares ◽  
...  

Investigating microbial interactions from an ecological perspective is a particularly fruitful approach to unveil both new chemistry and bioactivity. Microbial predator–prey interactions in particular rely on natural products as signal or defense molecules. In this context, we identified a grazing-resistant Pseudomonas strain, isolated from the bacterivorous amoeba Dictyostelium discoideum. Genome analysis of this bacterium revealed the presence of two biosynthetic gene clusters that were found adjacent to each other on a contiguous stretch of the bacterial genome. Although one cluster codes for the polyketide synthase producing the known antibiotic mupirocin, the other cluster encodes a nonribosomal peptide synthetase leading to the unreported cyclic lipopeptide jessenipeptin. We describe its complete structure elucidation, as well as its synergistic activity against methicillin-resistant Staphylococcus aureus, when in combination with mupirocin. Both biosynthetic gene clusters are regulated by quorum-sensing systems, with 3-oxo-decanoyl homoserine lactone (3-oxo-C10-AHL) and hexanoyl homoserine lactone (C6-AHL) being the respective signal molecules. This study highlights the regulation, richness, and complex interplay of bacterial natural products that emerge in the context of microbial competition.


2020 ◽  
Vol 21 (12) ◽  
Author(s):  
Fitria Ningsih ◽  
Dhian Chitra Ayu Fitria Sari ◽  
Shuhei Yabe ◽  
Akira Yokota ◽  
Wellyzar Sjamsuridzal

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.


2021 ◽  
Vol 1 (3) ◽  
pp. 573-585
Author(s):  
Hisayuki Komaki ◽  
Tomohiko Tamura

Streptomyces coelicolor A3(2) is used worldwide for genetic studies, and its complete genome sequence was published in 2002. However, as the whole genome of the type strain of S. coelicolor has not been analyzed, the relationship between S. coelicolor A3(2) and the type strain is not yet well known. To clarify differences in their biosynthetic potential, as well as their taxonomic positions, we sequenced whole genomes of S. coelicolor NBRC 12854T and type strains of its closely related species—such as Streptomyces daghestanicus, Streptomyces hydrogenans, and Streptomyces violascens—via PacBio. Biosynthetic gene clusters for polyketides and non-ribosomal peptides were surveyed by antiSMASH, followed by bioinformatic analyses. Type strains of Streptomyces albidoflavus, S. coelicolor, S. daghestanicus, S. hydrogenans, and S. violascens shared the same 16S rDNA sequence, but S. coelicolor A3(2) did not. S. coelicolor A3(2) and S. coelicolor NBRC 12854T can be classified as Streptomycesanthocyanicus and S. albidoflavus, respectively. In contrast, S. daghestanicus, S. hydrogenans, and S. violascens are independent species, despite their identical 16S rDNA sequences. S. coelicolor A3(2), S. coelicolor NBRC 12854T, S. daghestanicus NBRC 12762T, S. hydrogenans NBRC 13475T, and S. violascens NBRC 12920T each harbor specific polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) gene clusters in their genomes, whereas PKS and NRPS gene clusters are well conserved between S. coelicolor A3(2) and S. anthocyanicus JCM 5058T, and between S. coelicolor NBRC 12854T and S. albidoflavus DSM 40455T, belonging to the same species. These results support our hypothesis that the repertoires of PKS and NRPS gene clusters are different between different species.


2020 ◽  
Vol 9 (15) ◽  
Author(s):  
Ninfa Ramírez-Durán ◽  
Rafael R. de la Haba ◽  
Blanca Vera-Gargallo ◽  
Cristina Sánchez-Porro ◽  
Scarlett Alonso-Carmona ◽  
...  

The draft genome sequence of Saccharomonospora piscinae KCTC 19743T, with a size of 4,897,614 bp, was assembled into 11 scaffolds containing 4,561 open reading frames and a G+C content of 71.0 mol%. Polyketide synthase and nonribosomal peptide synthetase gene clusters, which are responsible for the biosynthesis of several biomolecules, were identified and located in different regions in the genome.


2020 ◽  
Vol 48 (8) ◽  
pp. e48-e48 ◽  
Author(s):  
Peng Xu ◽  
Cyrus Modavi ◽  
Benjamin Demaree ◽  
Frederick Twigg ◽  
Benjamin Liang ◽  
...  

Abstract Microbial biosynthetic gene clusters are a valuable source of bioactive molecules. However, because they typically represent a small fraction of genomic material in most metagenomic samples, it remains challenging to deeply sequence them. We present an approach to isolate and sequence gene clusters in metagenomic samples using microfluidic automated plasmid library enrichment. Our approach provides deep coverage of the target gene cluster, facilitating reassembly. We demonstrate the approach by isolating and sequencing type I polyketide synthase gene clusters from an Antarctic soil metagenome. Our method promotes the discovery of functional-related genes and biosynthetic pathways.


2020 ◽  
Vol 8 (12) ◽  
pp. 2034
Author(s):  
Nils Gummerlich ◽  
Yuriy Rebets ◽  
Constanze Paulus ◽  
Josef Zapp ◽  
Andriy Luzhetskyy

Natural products are an important source of novel investigational compounds in drug discovery. Especially in the field of antibiotics, Actinobacteria have been proven to be a reliable source for lead structures. The discovery of these natural products with activity- and structure-guided screenings has been impeded by the constant rediscovery of previously identified compounds. Additionally, a large discrepancy between produced natural products and biosynthetic potential in Actinobacteria, including representatives of the order Pseudonocardiales, has been revealed using genome sequencing. To turn this genomic potential into novel natural products, we used an approach including the in-silico pre-selection of unique biosynthetic gene clusters followed by their systematic heterologous expression. As a proof of concept, fifteen Saccharothrixespanaensis genomic library clones covering predicted biosynthetic gene clusters were chosen for expression in two heterologous hosts, Streptomyceslividans and Streptomycesalbus. As a result, two novel natural products, an unusual angucyclinone pentangumycin and a new type II polyketide synthase shunt product SEK90, were identified. After purification and structure elucidation, the biosynthetic pathways leading to the formation of pentangumycin and SEK90 were deduced using mutational analysis of the biosynthetic gene cluster and feeding experiments with 13C-labelled precursors.


2015 ◽  
Vol 3 (5) ◽  
Author(s):  
Hisayuki Komaki ◽  
Natsuko Ichikawa ◽  
Akira Hosoyama ◽  
Nobuyuki Fujita ◽  
Yasuhiro Igarashi

Here, we report the draft genome sequence of Streptomyces sp. TP-A0890, a producer of FR-900452 and A-74863a. The genome was found to contain at least eight polyketide synthase and nonribosomal peptide synthetase gene clusters. A prediction of gene functions based on the sequence similarity allowed us to assign the biosynthetic gene clusters for FR-900452 and A-74863a.


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