scholarly journals A Systematic Analysis of Mosquito-Microbiome Biosynthetic Gene Clusters Reveals Antimalarial Siderophores that Reduce Mosquito Reproduction Capacity

2020 ◽  
Vol 27 (7) ◽  
pp. 817-826.e5
Author(s):  
Jack G. Ganley ◽  
Ashmita Pandey ◽  
Kayla Sylvester ◽  
Kuan-Yi Lu ◽  
Maria Toro-Moreno ◽  
...  
Keyword(s):  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Systematic Analysis

scholarly journals Multigenome analysis implicates miniature inverted-repeat transposable elements (MITEs) in metabolic diversification in eudicots

2018 ◽  
Vol 115 (28) ◽  
pp. E6650-E6658 ◽  
Author(s):  
Alexander M. Boutanaev ◽  
Anne E. Osbourn
Keyword(s):  
Transposable Elements ◽  
Inverted Repeat ◽  
Cluster Formation ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Terpene Synthase ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Systematic Analysis ◽  
Plant Genomes

Plants produce a plethora of natural products, including many drugs. It has recently emerged that the genes encoding different natural product pathways may be organized as biosynthetic gene clusters in plant genomes, with >30 examples reported so far. Despite superficial similarities with microbes, these clusters have not arisen by horizontal gene transfer, but rather by gene duplication, neofunctionalization, and relocation via unknown mechanisms. Previously we reported that two Arabidopsis thaliana biosynthetic gene clusters are located in regions of the genome that are significantly enriched in transposable elements (TEs). Other plant biosynthetic gene clusters also harbor abundant TEs. TEs can mediate genomic rearrangement by providing homologous sequences that enable illegitimate recombination and gene relocation. Thus, TE-mediated recombination may contribute to plant biosynthetic gene cluster formation. TEs may also facilitate establishment of regulons. However, a systematic analysis of the TEs associated with plant biosynthetic gene clusters has not been carried out. Here we investigate the TEs associated with clustered terpene biosynthetic genes in multiple plant genomes and find evidence to suggest a role for miniature inverted-repeat transposable elements in cluster formation in eudicots. Through investigation of the newly sequenced Amborella trichopoda, Aquilegia coerulea, and Kalanchoe fedtschenkoi genomes, we further show that the “block” mechanism of founding of biosynthetic gene clusters through duplication and diversification of pairs of terpene synthase and cytochrome P450 genes that is prevalent in the eudicots arose around 90–130 million years ago, after the appearance of the basal eudicots and before the emergence of the superrosid clade.

scholarly journals A Systematic Analysis of Biosynthetic Gene Clusters in the Human Microbiome Reveals a Common Family of Antibiotics

Cell ◽  
2014 ◽  
Vol 158 (6) ◽  
pp. 1402-1414 ◽  
Author(s):  
Mohamed S. Donia ◽  
Peter Cimermancic ◽  
Christopher J. Schulze ◽  
Laura C. Wieland Brown ◽  
John Martin ◽  
...  
Keyword(s):  
Human Microbiome ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Systematic Analysis

scholarly journals A Systematic Analysis of Mosquito-Microbiome Biosynthetic Gene Clusters Reveals Antimalarial Siderophores that Reduce Mosquito Reproduction Capacity

2020 ◽  
Author(s):  
Jack G. Ganley ◽  
Ashmita Pandey ◽  
Kayla Sylvester ◽  
Kuan-Yi Lu ◽  
Maria Toro-Moreno ◽  
...  
Keyword(s):  
Small Molecules ◽  
Genetic Manipulation ◽  
Control Strategies ◽  
Gene Clusters ◽  
Blood Feeding ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Systematic Analysis ◽  
Depth Analysis

ABSTRACTAdvances in infectious disease control strategies through genetic manipulation of insect microbiomes have heightened interest in microbially produced small molecules within mosquitoes. Herein, 33 mosquito-associated bacterial genomes were mined and over 700 putative biosynthetic gene clusters (BGCs) were identified, 135 of which belong to known classes of BGCs. After an in-depth analysis of the 135 BGCs, iron-binding siderophores were chosen for further investigation due to their high abundance and well-characterized bioactivities. Through various metabolomic strategies, eight siderophore scaffolds were identified in six strains of mosquito-associated bacteria. Among these, serratiochelin A and pyochelin were found to reduce female Anopheles gambiae overall fecundity likely by lowering their blood feeding rate. Serratiochelin A and pyochelin were further found to inhibit the Plasmodium parasite asexual blood and liver stages in vitro. Our work supplies a bioinformatic resource for future mosquito microbiome studies and highlights an understudied source of bioactive small molecules.

scholarly journals mSphere of Influence: Systematically Decoding Microbial Chemical Communication

mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Laura A. Mike
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Global Analysis ◽  
Human Microbiome ◽  
Gene Clusters ◽  
Bacterial Pathogenesis ◽  
Biosynthetic Gene ◽  
Interspecies Interactions ◽  
Biosynthetic Gene Clusters ◽  
Systematic Analysis

ABSTRACT Laura A. Mike works in the field of bacterial pathogenesis. In this mSphere of Influence article, she reflects on how “Insights into Secondary Metabolism from a Global Analysis of Prokaryotic Biosynthetic Gene Clusters” by P. Cimermancic et al. (Cell 158:412–421, 2014, https://doi.org/10.1016/j.cell.2014.06.034) and “A Systematic Analysis of Biosynthetic Gene Clusters in the Human Microbiome Reveals a Common Family of Antibiotics” by M. S. Donia et al. (Cell 158:1402–1414, 2014, https://doi.org/10.1016/j.cell.2014.08.032) made an impact on her by systematically identifying microbiome-associated biosynthetic gene clusters predicted to synthesize secondary metabolites, which may facilitate interspecies interactions.

Expanding the Natural Products Heterologous Expression Repertoire in the Model Cyanobacterium Anabaena sp. Strain PCC 7120: Production of Pendolmycin and Teleocidin B-4

2019 ◽  
Author(s):  
Patrick Videau ◽  
Kaitlyn Wells ◽  
Arun Singh ◽  
Jessie Eiting ◽  
Philip Proteau ◽  
...  
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Gene Clusters ◽  
Combinatorial Biosynthesis ◽  
Test Case ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Cyanobacterium Anabaena ◽  
Anabaena Sp ◽  
Pcc 7120

Cyanobacteria are prolific producers of natural products and genome mining has shown that many orphan biosynthetic gene clusters can be found in sequenced cyanobacterial genomes. New tools and methodologies are required to investigate these biosynthetic gene clusters and here we present the use of <i>Anabaena </i>sp. strain PCC 7120 as a host for combinatorial biosynthesis of natural products using the indolactam natural products (lyngbyatoxin A, pendolmycin, and teleocidin B-4) as a test case. We were able to successfully produce all three compounds using codon optimized genes from Actinobacteria. We also introduce a new plasmid backbone based on the native <i>Anabaena</i>7120 plasmid pCC7120ζ and show that production of teleocidin B-4 can be accomplished using a two-plasmid system, which can be introduced by co-conjugation.

scholarly journals Global biogeographic sampling of bacterial secondary metabolism

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Zachary Charlop-Powers ◽  
Jeremy G Owen ◽  
Boojala Vijay B Reddy ◽  
Melinda A Ternei ◽  
Denise O Guimarães ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Genome Sequencing ◽  
Geographic Distance ◽  
Gene Clusters ◽  
Natural World ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Road Map ◽  
Two Factors ◽  
Natural Products Discovery

Recent bacterial (meta)genome sequencing efforts suggest the existence of an enormous untapped reservoir of natural-product-encoding biosynthetic gene clusters in the environment. Here we use the pyro-sequencing of PCR amplicons derived from both nonribosomal peptide adenylation domains and polyketide ketosynthase domains to compare biosynthetic diversity in soil microbiomes from around the globe. We see large differences in domain populations from all except the most proximal and biome-similar samples, suggesting that most microbiomes will encode largely distinct collections of bacterial secondary metabolites. Our data indicate a correlation between two factors, geographic distance and biome-type, and the biosynthetic diversity found in soil environments. By assigning reads to known gene clusters we identify hotspots of biomedically relevant biosynthetic diversity. These observations not only provide new insights into the natural world, they also provide a road map for guiding future natural products discovery efforts.

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