scholarly journals Bioactive Molecules from Mangrove Streptomyces qinglanensis 172205

Marine Drugs ◽  
2020 ◽  
Vol 18 (5) ◽  
pp. 255
Author(s):  
Dongbo Xu ◽  
Erli Tian ◽  
Fandong Kong ◽  
Kui Hong
Keyword(s):  
Gene Cluster ◽  
Secondary Metabolite ◽  
Biosynthetic Gene Cluster ◽  
Bioactive Molecules ◽  
Spectroscopic Methods ◽  
Biosynthetic Gene ◽  
Electronic Circular Dichroism ◽  
Chemical Structures ◽  
New Compounds ◽  
Antiproliferative Activities

Five new compounds 15R-17,18-dehydroxantholipin (1), (3E,5E,7E)-3-methyldeca-3,5,7-triene-2,9-dione (2) and qinlactone A–C (3–5) were identified from mangrove Streptomyces qinglanensis 172205 with “genetic dereplication,” which deleted the highly expressed secondary metabolite-enterocin biosynthetic gene cluster. The chemical structures were established by spectroscopic methods, and the absolute configurations were determined by electronic circular dichroism (ECD). Compound 1 exhibited strong anti-microbial and antiproliferative bioactivities, while compounds 2–4 showed weak antiproliferative activities.

Identification of the kinanthraquinone biosynthetic gene cluster by expression of an atypical response regulator

2021 ◽  
Vol 85 (3) ◽  
pp. 714-721
Author(s):  
Risa Takao ◽  
Katsuyuki Sakai ◽  
Hiroyuki Koshino ◽  
Hiroyuki Osada ◽  
Shunji Takahashi
Keyword(s):  
Heterologous Expression ◽  
Gene Cluster ◽  
Secondary Metabolite ◽  
Response Regulator ◽  
Bac Library ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Gene Organization ◽  
Biosynthetic Gene ◽  
Streptomyces Sp

ABSTRACT Recent advances in genome sequencing have revealed a variety of secondary metabolite biosynthetic gene clusters in actinomycetes. Understanding the biosynthetic mechanism controlling secondary metabolite production is important for utilizing these gene clusters. In this study, we focused on the kinanthraquinone biosynthetic gene cluster, which has not been identified yet in Streptomyces sp. SN-593. Based on chemical structure, 5 type II polyketide synthase gene clusters were listed from the genome sequence of Streptomyces sp. SN-593. Among them, a candidate gene cluster was selected by comparing the gene organization with grincamycin, which is synthesized through an intermediate similar to kinanthraquinone. We initially utilized a BAC library for subcloning the kiq gene cluster, performed heterologous expression in Streptomyces lividans TK23, and identified the production of kinanthraquinone and kinanthraquinone B. We also found that heterologous expression of kiqA, which belongs to the DNA-binding response regulator OmpR family, dramatically enhanced the production of kinanthraquinones.

scholarly journals Trichoderma reesei Contains a Biosynthetic Gene Cluster That Encodes the Antifungal Agent Ilicicolin H

2021 ◽  
Vol 7 (12) ◽  
pp. 1034
Author(s):  
Mary L. Shenouda ◽  
Maria Ambilika ◽  
Russell J. Cox
Keyword(s):  
Cytochrome P450 ◽  
Gene Cluster ◽  
Trichoderma Reesei ◽  
Antifungal Agent ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Fungal Host ◽  
Tetramic Acids ◽  
New Compounds

The trili biosynthetic gene cluster (BGC) from the well-studied organism Trichoderma reesei was studied by heterologous expression in the fungal host Aspergillus oryzae. Coexpression of triliA and triliB produces two new acyl tetramic acids. Addition of the ring-expanding cytochrome P450 encoded by triliC then yields a known pyridone intermediate to ilicicolin H and a new chain-truncated shunt metabolite. Finally, addition of the intramolecular Diels-Alderase encoded by triliD affords a mixture of 8-epi ilicicolin H and ilicicolin H itself, showing that the T. reesei trili BGC encodes biosynthesis of this potent antifungal agent. Unexpected A. oryzae shunt pathways are responsible for the production of the new compounds, emphasising the role of fungal hosts in catalysing diversification reactions.

scholarly journals Heterologous Expression of the Unusual Terreazepine Biosynthetic Gene Cluster Reveals a Promising Approach for Identifying New Chemical Scaffolds

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Lindsay K. Caesar ◽  
Matthew T. Robey ◽  
Michael Swyers ◽  
Md N. Islam ◽  
Rosa Ye ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Secondary Metabolite ◽  
Heterologous Gene Expression ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Metabolic Enzyme ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Artificial Chromosomes ◽  
Indoleamine 2,3 Dioxygenase

ABSTRACT Advances in genome sequencing have revitalized natural product discovery efforts, revealing the untapped biosynthetic potential of fungi. While the volume of genomic data continues to expand, discovery efforts are slowed due to the time-consuming nature of experiments required to characterize new molecules. To direct efforts toward uncharacterized biosynthetic gene clusters most likely to encode novel chemical scaffolds, we took advantage of comparative metabolomics and heterologous gene expression using fungal artificial chromosomes (FACs). By linking mass spectral profiles with structural clues provided by FAC-encoded gene clusters, we targeted a compound originating from an unusual gene cluster containing an indoleamine 2,3-dioxygenase (IDO). With this approach, we isolate and characterize R and S forms of the new molecule terreazepine, which contains a novel chemical scaffold resulting from cyclization of the IDO-supplied kynurenine. The discovery of terreazepine illustrates that FAC-based approaches targeting unusual biosynthetic machinery provide a promising avenue forward for targeted discovery of novel scaffolds and their biosynthetic enzymes, and it also represents another example of a biosynthetic gene cluster “repurposing” a primary metabolic enzyme to diversify its secondary metabolite arsenal. IMPORTANCE Here, we provide evidence that Aspergillus terreus encodes a biosynthetic gene cluster containing a repurposed indoleamine 2,3-dioxygenase (IDO) dedicated to secondary metabolite synthesis. The discovery of this neofunctionalized IDO not only enabled discovery of a new compound with an unusual chemical scaffold but also provided insight into the numerous strategies fungi employ for diversifying and protecting themselves against secondary metabolites. The observations in this study set the stage for further in-depth studies into the function of duplicated IDOs present in fungal biosynthetic gene clusters and presents a strategy for accessing the biosynthetic potential of gene clusters containing duplicated primary metabolic genes.

scholarly journals Microfluidic automated plasmid library enrichment for biosynthetic gene cluster discovery

2020 ◽  
Vol 48 (8) ◽  
pp. e48-e48 ◽  
Author(s):  
Peng Xu ◽  
Cyrus Modavi ◽  
Benjamin Demaree ◽  
Frederick Twigg ◽  
Benjamin Liang ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Polyketide Synthase ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Bioactive Molecules ◽  
Type I ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Plasmid Library ◽  
Polyketide Synthase Gene

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.

scholarly journals Beyond the Biosynthetic Gene Cluster Paradigm: Genome-Wide Coexpression Networks Connect Clustered and Unclustered Transcription Factors to Secondary Metabolic Pathways

2021 ◽  
Author(s):  
Min Jin Kwon ◽  
Charlotte Steiniger ◽  
Timothy C. Cairns ◽  
Jennifer H. Wisecaver ◽  
Abigail L. Lind ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Secondary Metabolites ◽  
Gene Cluster ◽  
Metabolic Pathways ◽  
Biosynthetic Gene Cluster ◽  
Bioactive Molecules ◽  
Biosynthetic Gene ◽  
Genome Wide ◽  
Coexpression Networks

There is an urgent need for novel bioactive molecules in both agriculture and medicine. The genomes of fungi are thought to contain vast numbers of metabolic pathways involved in the biosynthesis of secondary metabolites with diverse bioactivities.

Anacyclamide D8P, a prenylated cyanobactin from a Sphaerospermopsis sp. cyanobacterium

2017 ◽  
Author(s):  
Joana Martins ◽  
Niina Leikoski ◽  
Matti Wahlsten ◽  
Joana Azevedo ◽  
Jorge Antunes ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Cyclic Peptides ◽  
Biosynthetic Gene Cluster ◽  
The Novel ◽  
Tyrosine Residue ◽  
Biosynthetic Gene ◽  
Post Translational Modification ◽  
Biological Assays ◽  
Mass Spectrometric Data ◽  
Spectrometric Data

Cyanobactins are a family of linear and cyclic peptides produced through the post-translational modification of short precursor peptides. Anacyclamides are macrocyclic cyanobactins with a highly diverse sequence that are common in the genus <i>Anabaena</i>. A mass spectrometry-based screening of potential cyanobactin producers led to the discovery of a new prenylated member of this family of compounds, anacyclamide D8P (<b>1</b>), from <i>Sphaerospermopsis</i> sp. LEGE 00249. The anacyclamide biosynthetic gene cluster (<i>acy</i>) encoding the novel macrocyclic prenylated cyanobactin, was sequenced. Heterologous expression of the acy gene cluster in <i>Escherichia</i> <i>coli</i> established the connection between genomic and mass spectrometric data. Unambiguous establishment of the type and site of prenylation required the full structural elucidation of <b>1</b> using Nuclear Magnetic Resonance (NMR), which demonstrated that a forward prenylation occurred on the tyrosine residue. Compound <b>1</b> was tested in pharmacologically or ecologically relevant biological assays and revealed moderate antimicrobial activity towards the fouling bacterium <i>Halomonas aquamarina</i> CECT 5000.<br>

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