scholarly journals Streptomyces lydicamycinicus sp. nov. and Its Secondary Metabolite Biosynthetic Gene Clusters for Polyketide and Nonribosomal Peptide Compounds

2020 ◽  
Vol 8 (3) ◽  
pp. 370
Author(s):  
Hisayuki Komaki ◽  
Akira Hosoyama ◽  
Yasuhiro Igarashi ◽  
Tomohiko Tamura

(1) Background: Streptomyces sp. TP-A0598 derived from seawater produces lydicamycin and its congeners. We aimed to investigate its taxonomic status; (2) Methods: A polyphasic approach and whole genome analysis are employed; (3) Results: Strain TP-A0598 contained ll-diaminopimelic acid, glutamic acid, glycine, and alanine in its peptidoglycan. The predominant menaquinones were MK-9(H6) and MK-9(H8), and the major fatty acids were C16:0, iso-C15:0, iso-C16:0, and anteiso-C15:0. Streptomyces sp. TP-A0598 showed a 16S rDNA sequence similarity value of 99.93% (1 nucleottide difference) to Streptomyces angustmyceticus NRRL B-2347T. The digital DNA–DNA hybridisation value between Streptomyces sp. TP-A0598 and its closely related type strains was 25%–46%. Differences in phenotypic characteristics between Streptomyces sp. TP-A0598 and its phylogenetically closest relative, S. angustmyceticus NBRC 3934T, suggested strain TP-A0598 to be a novel species. Streptomyces sp. TP-A0598 and S. angustmyceticus NBRC 3934T harboured nine and 13 biosynthetic gene clusters for polyketides and nonribosomal peptides, respectively, among which only five clusters were shared between them, whereas the others are specific for each strain; and (4) Conclusions: For strain TP-A0598, the name Streptomyces lydicamycinicus sp. nov. is proposed; the type strain is TP-A0598T (=NBRC 110027T).

2021 ◽  
Vol 12 ◽  
Author(s):  
Carlos Caicedo-Montoya ◽  
Monserrat Manzo-Ruiz ◽  
Rigoberto Ríos-Estepa

Species of the genus Streptomyces are known for their ability to produce multiple secondary metabolites; their genomes have been extensively explored to discover new bioactive compounds. The richness of genomic data currently available allows filtering for high quality genomes, which in turn permits reliable comparative genomics studies and an improved prediction of biosynthetic gene clusters (BGCs) through genome mining approaches. In this work, we used 121 genome sequences of the genus Streptomyces in a comparative genomics study with the aim of estimating the genomic diversity by protein domains content, sequence similarity of proteins and conservation of Intergenic Regions (IGRs). We also searched for BGCs but prioritizing those with potential antibiotic activity. Our analysis revealed that the pan-genome of the genus Streptomyces is clearly open, with a high quantity of unique gene families across the different species and that the IGRs are rarely conserved. We also described the phylogenetic relationships of the analyzed genomes using multiple markers, obtaining a trustworthy tree whose relationships were further validated by Average Nucleotide Identity (ANI) calculations. Finally, 33 biosynthetic gene clusters were detected to have potential antibiotic activity and a predicted mode of action, which might serve up as a guide to formulation of related experimental studies.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hooi-Leng Ser ◽  
Loh Teng-Hern Tan ◽  
Wen-Si Tan ◽  
Wai-Fong Yin ◽  
Kok-Gan Chan

The contribution of streptomycetes to human health is undeniably important and significant, given that these filamentous microbes can produce interesting compounds that can be used to cure deadly infections and even cancer. Isolated from the east coast of Peninsular Malaysia, Streptomyces sp. MUSC 14 has shown significant antioxidant capacity. The current study explores the genomic potential of MUSC 14 via a genome mining approach. The genome size of MUSC 14 is 10,274,825 bp with G + C content of 71.3 %. AntiSMASH analysis revealed a total of nine biosynthetic gene clusters (with more than 80 % similarities to known gene clusters). This information serves as an important foundation for subsequent studies, particularly the purification and isolation of bioactive compounds by genetic manipulation techniques.


2021 ◽  
Author(s):  
Aman S. Imani ◽  
Aileen R. Lee ◽  
Nisha Vishwanathan ◽  
Floris de Waal ◽  
Michael F. Freeman

Borosins are ribosomally synthesized and post-translationally modified peptides (RiPPs) with α-N-methylations installed on the peptide backbone that impart unique properties like proteolytic stability to these natural products. The borosin RiPP family was initially reported only in fungi until our recent discovery and characterization of a Type IV split borosin system in the metal-respiring bacterium Shewanella oneidensis. Here, we used hidden Markov models and sequence similarity networks to identify over 1,600 putative pathways that show split borosin biosynthetic gene clusters are widespread in bacteria. Noteworthy differences in precursor and α-N-methyltransferase open reading frame sizes, architectures, and core peptide properties allow further subdivision of the borosin family into six additional discrete structural types, of which five have been validated in this study.


Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6580
Author(s):  
Charlotte Beck ◽  
Tetiana Gren ◽  
Francisco Javier Ortiz-López ◽  
Tue Sparholt Jørgensen ◽  
Daniel Carretero-Molina ◽  
...  

Streptomyces are well-known producers of a range of different secondary metabolites, including antibiotics and other bioactive compounds. Recently, it has been demonstrated that “silent” biosynthetic gene clusters (BGCs) can be activated by heterologously expressing transcriptional regulators from other BGCs. Here, we have activated a silent BGC in Streptomyces sp. CA-256286 by overexpression of a set of SARP family transcriptional regulators. The structure of the produced compound was elucidated by NMR and found to be an N-acetyl cysteine adduct of the pyranonaphtoquinone polyketide 3′-O-α-d-forosaminyl-(+)-griseusin A. Employing a combination of multi-omics and metabolic engineering techniques, we identified the responsible BGC. These methods include genome mining, proteomics and transcriptomics analyses, in combination with CRISPR induced gene inactivations and expression of the BGC in a heterologous host strain. This work demonstrates an easy-to-implement workflow of how silent BGCs can be activated, followed by the identification and characterization of the produced compound, the responsible BGC, and hints of its biosynthetic pathway.


Author(s):  
Jun Sik Ra ◽  
Min Ji Kim ◽  
Dong Hyeon Lee ◽  
Ji Won Jeong ◽  
Seung Bum Kim

An actinobacterial strain designated MMS20-R1-14T was isolated from a riverside soil sample. Colonies on agar plates were orange to strong orange brown in colour, which later became black. The cells grew at 10–40 °C (optimum, 37 °C), pH 5.0–11.0 (pH 8.0) and in the presence of 0–4 % NaCl (1 %). The 16S rRNA gene sequence of strain MMS20-R1-14T showed highest similarities to Micromonospora wenchangensis CCTCC AA 2012002T (99.51 %) and Micromonospora rifamycinica AM105T (99.37 %). The orthoANI values between strain MMS20-R1-14T and the two type strains were 95.72 and 90.99 %, and the digital DNA–DNA hybridization values were 63.6 and 40.8 %, respectively, thus confirming the distinction of strain MMS20-R1-14T from its mostly related species. The DNA G+C content of strain MMS20-R1-14T was 72.9 mol%. The strain contained meso-diaminopimelic acid as the major cell-wall amino acid, and the characteristic whole-cell sugars were arabinose, xylose, glucose, ribose and rhamnose. The main cellular fatty acids were C18 : 1  ω9c, iso-C15 : 0 and iso-C16 : 0, the diagnostic polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine, and the predominant menaquinones were MK-10(H4) and MK-10(H6), all of which were consistent with those of Micromonospora . Strain MMS20-R1-14T showed antimicrobial activity against a range of bacterial and yeast species. The genome of the strain was found to contain 33 potential biosynthetic gene clusters for secondary metabolites, thus showing a high potential as a producer of bioactive compounds. On the basis of these phenotypic, genotypic and chemotaxonomic data, strain MMS20-R1-14T merits recognition as representing a novel species of the genus Micromonospora , for which the name Micromonospora humida sp. nov. (type strain=MMS20 R1-14T=KCTC 49541T=JCM 34494T) is proposed.


2017 ◽  
Vol 20 (4) ◽  
pp. 1103-1113 ◽  
Author(s):  
Kai Blin ◽  
Hyun Uk Kim ◽  
Marnix H Medema ◽  
Tilmann Weber

Abstract Many drugs are derived from small molecules produced by microorganisms and plants, so-called natural products. Natural products have diverse chemical structures, but the biosynthetic pathways producing those compounds are often organized as biosynthetic gene clusters (BGCs) and follow a highly conserved biosynthetic logic. This allows for the identification of core biosynthetic enzymes using genome mining strategies that are based on the sequence similarity of the involved enzymes/genes. However, mining for a variety of BGCs quickly approaches a complexity level where manual analyses are no longer possible and require the use of automated genome mining pipelines, such as the antiSMASH software. In this review, we discuss the principles underlying the predictions of antiSMASH and other tools and provide practical advice for their application. Furthermore, we discuss important caveats such as rule-based BGC detection, sequence and annotation quality and cluster boundary prediction, which all have to be considered while planning for, performing and analyzing the results of genome mining studies.


2019 ◽  
Vol 7 (6) ◽  
pp. 181 ◽  
Author(s):  
Katherine Gregory ◽  
Laura A. Salvador ◽  
Shukria Akbar ◽  
Barbara I. Adaikpoh ◽  
D. Cole Stevens

Coinciding with the increase in sequenced bacteria, mining of bacterial genomes for biosynthetic gene clusters (BGCs) has become a critical component of natural product discovery. The order Myxococcales, a reputable source of biologically active secondary metabolites, spans three suborders which all include natural product producing representatives. Utilizing the BiG-SCAPE-CORASON platform to generate a sequence similarity network that contains 994 BGCs from 36 sequenced myxobacteria deposited in the antiSMASH database, a total of 843 BGCs with lower than 75% similarity scores to characterized clusters within the MIBiG database are presented. This survey provides the biosynthetic diversity of these BGCs and an assessment of the predicted chemical space yet to be discovered. Considering the mere snapshot of myxobacteria included in this analysis, these untapped BGCs exemplify the potential for natural product discovery from myxobacteria.


2019 ◽  
Vol 8 (4) ◽  
Author(s):  
Janina Krause ◽  
Shanti Ratnakomala ◽  
Puspita Lisdiyanti ◽  
Regina Ort-Winklbauer ◽  
Wolfgang Wohlleben ◽  
...  

Streptomyces sp. strain I6 is a novel strain isolated from an Indonesian mangrove sediment sample. Bioinformatic analysis of the genome sequence of Streptomyces sp. I6 revealed 23 biosynthetic gene clusters.


2021 ◽  
Vol 22 (14) ◽  
pp. 7567
Author(s):  
Erik Mingyar ◽  
Lucas Mühling ◽  
Andreas Kulik ◽  
Anika Winkler ◽  
Daniel Wibberg ◽  
...  

By culturing microorganisms under standard laboratory conditions, most biosynthetic gene clusters (BGCs) are not expressed, and thus, the products are not produced. To explore this biosynthetic potential, we developed a novel “semi-targeted” approach focusing on activating “silent” BGCs by concurrently introducing a group of regulator genes into streptomycetes of the Tübingen strain collection. We constructed integrative plasmids containing two classes of regulatory genes under the control of the constitutive promoter ermE*p (cluster situated regulators (CSR) and Streptomyces antibiotic regulatory proteins (SARPs)). These plasmids were introduced into Streptomyces sp. TÜ17, Streptomyces sp. TÜ10 and Streptomyces sp. TÜ102. Introduction of the CSRs-plasmid into strain S. sp. TÜ17 activated the production of mayamycin A. By using the individual regulator genes, we proved that Aur1P, was responsible for the activation. In strain S. sp. TÜ102, the introduction of the SARP-plasmid triggered the production of a chartreusin-like compound. Insertion of the CSRs-plasmid into strain S. sp. TÜ10 resulted in activating the warkmycin-BGC. In both recombinants, activation of the BGCs was only possible through the simultaneous expression of aur1PR3 and griR in S. sp. TÜ102 and aur1P and pntR in of S. sp. TÜ10.


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