scholarly journals Genome and Metabolome MS-Based Mining of a Marine Strain of Aspergillus affinis

2021 ◽  
Vol 7 (12) ◽  
pp. 1091
Author(s):  
Micael F. M. Gonçalves ◽  
Sandra Hilário ◽  
Marta Tacão ◽  
Yves Van de Van de Peer ◽  
Artur Alves ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Sea Water ◽  
Gene Clusters ◽  
Pyroglutamic Acid ◽  
Biosynthetic Gene Clusters ◽  
Metabolite Profiles ◽  
In Series ◽  
Strain Type ◽  
Marine Strain ◽  
Hydroxybenzyl Alcohol

Aspergillus section Circumdati encompasses several species that express both beneficial (e.g., biochemical transformation of steroids and alkaloids, enzymes and metabolites) and harmful compounds (e.g., production of ochratoxin A (OTA)). Given their relevance, it is important to analyze the genetic and metabolic diversity of the species of this section. We sequenced the genome of Aspergillus affinis CMG 70, isolated from sea water, and compared it with the genomes of species from section Circumdati, including A. affinis’s strain type. The A. affinis genome was characterized considering secondary metabolites biosynthetic gene clusters (BGCs), carbohydrate-active enzymes (CAZymes), and transporters. To uncover the biosynthetic potential of A. affinis CMG 70, an untargeted metabolomics (LC-MS/MS) approach was used. Cultivating the fungus in the presence and absence of sea salt showed that A. affinis CMG 70 metabolite profiles are salt dependent. Analyses of the methanolic crude extract revealed the presence of both unknown and well-known Aspergillus compounds, such as ochratoxin A, anti-viral (e.g., 3,5-Di-tert-butyl-4-hydroxybenzoic acid and epigallocatechin), anti-bacterial (e.g., 3-Hydroxybenzyl alcohol, L-pyroglutamic acid, lecanoric acid), antifungal (e.g., L-pyroglutamic acid, 9,12,13-Trihydroxyoctadec-10-enoic acid, hydroxyferulic acid), and chemotherapeutic (e.g., daunomycinone, mitoxantrone) related metabolites. Comparative analysis of 17 genomes from 16 Aspergillus species revealed abundant CAZymes (568 per species), secondary metabolite BGCs (73 per species), and transporters (1359 per species). Some BGCs are highly conserved in this section (e.g., pyranonigrin E and UNII-YC2Q1O94PT (ACR toxin I)), while others are incomplete or completely lost among species (e.g., bikaverin and chaetoglobosins were found exclusively in series Sclerotiorum, while asperlactone seemed completely lost). The results of this study, including genome analysis and metabolome characterization, emphasize the molecular diversity of A. affinis CMG 70, as well as of other species in the section Circumdati.

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.

scholarly journals Multi-omics profiling of Earth's biomes reveals that microbial and metabolite composition are shaped by the environment

2021 ◽  
Author(s):  
Justin P Shaffer ◽  
Louis-Félix Nothias ◽  
Luke R Thompson ◽  
Sanders G Jon ◽  
Rodolfo A Salido ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Microbial Communities ◽  
Gene Clusters ◽  
Metagenomic Data ◽  
Biosynthetic Gene Clusters ◽  
Metabolic Potential ◽  
Metagenome Analysis ◽  
Metabolite Profiles ◽  
Integrated Omics ◽  
Chemical Evidence

Microbes produce an array of secondary metabolites that perform diverse functions from communication to defense. These metabolites have been used to benefit human health and sustainability. In their analysis of the Genomes from Earth's Microbiomes (GEM) catalog, Nayfach and co-authors observed that, whereas genes coding for certain classes of secondary metabolites are limited or enriched in certain microbial taxa, "specific chemistry is not limited or amplified by the environment, and that most classes of secondary metabolites can be found nearly anywhere". Although metagenome mining is a powerful way to annotate biosynthetic gene clusters (BCGs), chemical evidence is required to confirm the presence of metabolites and comprehensively address this fundamental hypothesis, as metagenomic data only identify metabolic potential. To describe the Earth's metabolome, we use an integrated omics approach: the direct survey of metabolites associated with microbial communities spanning diverse environments using untargeted metabolomics coupled with metagenome analysis. We show, in contrast to Nayfach and co-authors, that the presence of certain classes of secondary metabolites can be limited or amplified by the environment. Importantly, our data indicate that considering the relative abundances of secondary metabolites (i.e., rather than only presence/absence) strengthens differences in metabolite profiles across environments, and that their richness and composition in any given sample do not directly reflect those of co-occurring microbial communities, but rather vary with the environment.

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.

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.

Challenges of functional expression of complex polyketide biosynthetic gene clusters

2021 ◽  
Vol 69 ◽  
pp. 103-111
Author(s):  
Yaojie Gao ◽  
Yuchun Zhao ◽  
Xinyi He ◽  
Zixin Deng ◽  
Ming Jiang
Keyword(s):  
Gene Clusters ◽  
Functional Expression ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters

scholarly journals Identification of a New Antimicrobial, Desertomycin H, Utilizing a Modified Crowded Plate Technique

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 424
Author(s):  
Osama G. Mohamed ◽  
Sadaf Dorandish ◽  
Rebecca Lindow ◽  
Megan Steltz ◽  
Ifrah Shoukat ◽  
...  
Keyword(s):  
Antibiotic Production ◽  
Gene Clusters ◽  
Multidrug Resistant ◽  
Microbial Interactions ◽  
Mass Spectrometry Data ◽  
Metagenomic Data ◽  
Resistant Bacteria ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Plate Technique

The antibiotic-resistant bacteria-associated infections are a major global healthcare threat. New classes of antimicrobial compounds are urgently needed as the frequency of infections caused by multidrug-resistant microbes continues to rise. Recent metagenomic data have demonstrated that there is still biosynthetic potential encoded in but transcriptionally silent in cultivatable bacterial genomes. However, the culture conditions required to identify and express silent biosynthetic gene clusters that yield natural products with antimicrobial activity are largely unknown. Here, we describe a new antibiotic discovery scheme, dubbed the modified crowded plate technique (mCPT), that utilizes complex microbial interactions to elicit antimicrobial production from otherwise silent biosynthetic gene clusters. Using the mCPT as part of the antibiotic crowdsourcing educational program Tiny Earth®, we isolated over 1400 antibiotic-producing microbes, including 62, showing activity against multidrug-resistant pathogens. The natural product extracts generated from six microbial isolates showed potent activity against vancomycin-intermediate resistant Staphylococcus aureus. We utilized a targeted approach that coupled mass spectrometry data with bioactivity, yielding a new macrolactone class of metabolite, desertomycin H. In this study, we successfully demonstrate a concept that significantly increased our ability to quickly and efficiently identify microbes capable of the silent antibiotic production.

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