scholarly journals A Regulator Based “Semi-Targeted” Approach to Activate Silent Biosynthetic Gene Clusters

2021 ◽  
Vol 22 (14) ◽  
pp. 7567
Author(s):  
Erik Mingyar ◽  
Lucas Mühling ◽  
Andreas Kulik ◽  
Anika Winkler ◽  
Daniel Wibberg ◽  
...  
Keyword(s):  
Gene Clusters ◽  
Regulatory Proteins ◽  
Biosynthetic Gene ◽  
Standard Laboratory ◽  
Biosynthetic Gene Clusters ◽  
Streptomyces Sp ◽  
Strain Collection ◽  
Regulator Genes ◽  
The Individual ◽  
Targeted Approach

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.

Biosynthetic strategies for tetramic acid formation

2021 ◽  
Author(s):  
Xuhua Mo ◽  
Tobias A. M. Gulder
Keyword(s):  
Molecular Mechanism ◽  
Gene Clusters ◽  
Acid Formation ◽  
Biosynthetic Gene ◽  
Tetramic Acid ◽  
Biosynthetic Gene Clusters ◽  
The Individual ◽  
First Time ◽  
Acid Unit

Over 30 biosynthetic gene clusters for natural tetramate have been identified. This highlight reviews the biosynthetic strategies for formation of tetramic acid unit for the first time, discussing the individual molecular mechanism in detail.

scholarly journals Whole-genome sequence of bioactive streptomycete derived from mangrove forest in Malaysia, Streptomyces sp. MUSC 14

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hooi-Leng Ser ◽  
Loh Teng-Hern Tan ◽  
Wen-Si Tan ◽  
Wai-Fong Yin ◽  
Kok-Gan Chan
Keyword(s):  
East Coast ◽  
Genetic Manipulation ◽  
Genome Mining ◽  
Gene Clusters ◽  
Peninsular Malaysia ◽  
Whole Genome Sequence ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Streptomyces Sp ◽  
A Genome

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.

scholarly journals Activation and Identification of a Griseusin Cluster in Streptomyces sp. CA-256286 by Employing Transcriptional Regulators and Multi-Omics Methods

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6580
Author(s):  
Charlotte Beck ◽  
Tetiana Gren ◽  
Francisco Javier Ortiz-López ◽  
Tue Sparholt Jørgensen ◽  
Daniel Carretero-Molina ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
Genome Mining ◽  
Gene Clusters ◽  
Transcriptional Regulators ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Heterologous Host ◽  
Streptomyces Sp ◽  
Identification And Characterization

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.

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
Keyword(s):  
Sequence Similarity ◽  
Taxonomic Status ◽  
Gene Clusters ◽  
Diaminopimelic Acid ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Whole Genome Analysis ◽  
16S Rdna Sequence ◽  
Streptomyces Sp ◽  
Type Strains

(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).

scholarly journals Complete Genome Sequence of the Putative Phosphonate Producer Streptomyces sp. Strain I6, Isolated from Indonesian Mangrove Sediment

2019 ◽  
Vol 8 (4) ◽  
Author(s):  
Janina Krause ◽  
Shanti Ratnakomala ◽  
Puspita Lisdiyanti ◽  
Regina Ort-Winklbauer ◽  
Wolfgang Wohlleben ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Sediment Sample ◽  
Gene Clusters ◽  
Bioinformatic Analysis ◽  
Mangrove Sediment ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Content Type ◽  
Streptomyces Sp

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.

scholarly journals Genome Sequence of Streptomyces sp. Strain HB-N217, Isolated from the Marine Sponge Forcepia sp.

2021 ◽  
Vol 10 (8) ◽  
Author(s):  
René K. M. Xavier ◽  
Dongbo Xu ◽  
Peter J. McCarthy ◽  
Shengming Yang ◽  
Guojun Wang
Keyword(s):  
Secondary Metabolites ◽  
Natural Product ◽  
Genome Sequence ◽  
Association Studies ◽  
Gene Clusters ◽  
Marine Natural Product ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Streptomyces Sp ◽  
Product Chemistry

ABSTRACT The genome sequence of the Forcepia sponge-derived bacterium Streptomyces sp. strain HB-N217 was determined, with approximately 8.25 Mbp and a G+C content of 72.1%. Thirty biosynthetic gene clusters that bear the capability to produce secondary metabolites were predicted. The results will aid marine natural product chemistry and sponge-microbe association studies.

scholarly journals Draft Genome Sequences of Two Polycyclic Tetramate Macrolactam Producers, Streptomyces sp. Strains JV180 and SP18CM02

2020 ◽  
Vol 9 (50) ◽  
Author(s):  
Yunci Qi ◽  
Keshav K. Nepal ◽  
Jennifer Greif ◽  
Cole Martini ◽  
Chad Tomlinson ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Draft Genome ◽  
Streptomyces Griseus ◽  
Gene Clusters ◽  
Gene Content ◽  
Biosynthetic Gene ◽  
Genome Sequences ◽  
Biosynthetic Gene Clusters ◽  
Content Type ◽  
Streptomyces Sp

ABSTRACT Here, we report the draft genome sequences of two related Streptomyces sp. strains, JV180 and SP18CM02. Despite their isolation from soils in Connecticut and Missouri (USA), respectively, they are strikingly similar in gene content. Both belong to the Streptomyces griseus clade and harbor several secondary metabolite biosynthetic gene clusters.

scholarly journals Complete Genome Sequence of the Filamentous Fungus Aspergillus westerdijkiae Reveals the Putative Biosynthetic Gene Cluster of Ochratoxin A

2016 ◽  
Vol 4 (5) ◽  
Author(s):  
Alolika Chakrabortti ◽  
Jinming Li ◽  
Zhao-Xun Liang
Keyword(s):  
Gene Cluster ◽  
Ochratoxin A ◽  
Complete Genome ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Regulatory Proteins ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Aspergillus Westerdijkiae ◽  
Major Producer

Ochratoxin A (OTA) is a common mycotoxin that contaminates food and agricultural products. Sequencing of the complete genome of Aspergillus westerdijkiae , a major producer of OTA , reveals more than 50 biosynthetic gene clusters, including a putative OTA biosynthetic gene cluster that encodes a dozen of enzymes, transporters, and regulatory proteins.

Draft genome and secondary metabolite biosynthetic gene clusters of Streptomyces sp. strain 196

2020 ◽  
Vol 47 (9) ◽  
pp. 6741-6747
Author(s):  
Prateek Kumar ◽  
Anjali Chauhan ◽  
Munendra Kumar ◽  
Bijoy K. Kuanr ◽  
Renu Solanki ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Draft Genome ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Streptomyces Sp
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