Lichen Biosynthetic Gene Clusters. Part I. Genome Sequencing Reveals a Rich Biosynthetic Potential

2018 ◽  
Vol 81 (4) ◽  
pp. 723-731 ◽  
Author(s):  
Robert L. Bertrand ◽  
Mona Abdel-Hameed ◽  
John L. Sorensen
Keyword(s):  
Genome Sequencing ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters

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.

scholarly journals Genome Sequencing and analyses of Two Marine Fungi from the North Sea Unraveled a Plethora of Novel Biosynthetic Gene Clusters

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Abhishek Kumar ◽  
Jens Laurids Sørensen ◽  
Frederik Teilfeldt Hansen ◽  
Mikko Arvas ◽  
Muhammad Fahad Syed ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
North Sea ◽  
Marine Fungi ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
The North ◽  
The North Sea

scholarly journals Tapping Into Actinobacterial Genomes for Natural Product Discovery

2021 ◽  
Vol 12 ◽  
Author(s):  
Tanim Arpit Singh ◽  
Ajit Kumar Passari ◽  
Anjana Jajoo ◽  
Sheetal Bhasin ◽  
Vijai Kumar Gupta ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Genome Sequencing ◽  
Genetic Regulation ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Bioactive Molecules ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Genomic Approach ◽  
New Gateway

The presence of secondary metabolite biosynthetic gene clusters (BGCs) makes actinobacteria well-known producers of diverse metabolites. These ubiquitous microbes are extensively exploited for their ability to synthesize diverse secondary metabolites. The extent of their ability to synthesize various molecules is yet to be evaluated. Current advancements in genome sequencing, metabolomics, and bioinformatics have provided a plethora of information about the mechanism of synthesis of these bioactive molecules. Accessing the biosynthetic gene cluster responsible for the production of metabolites has always been a challenging assignment. The genomic approach developments have opened a new gateway for examining and manipulating novel antibiotic gene clusters. These advancements have now developed a better understanding of actinobacterial physiology and their genetic regulation for the prolific production of natural products. These new approaches provide a unique opportunity to discover novel bioactive compounds that might replenish antibiotics’ exhausted stock and counter the microbes’ resistance crisis.

scholarly journals Secondary metabolites from hypocrealean entomopathogenic fungi: genomics as a tool to elucidate the encoded parvome

2020 ◽  
Vol 37 (9) ◽  
pp. 1164-1180 ◽  
Author(s):  
Liwen Zhang ◽  
Qun Yue ◽  
Chen Wang ◽  
Yuquan Xu ◽  
István Molnár
Keyword(s):  
Secondary Metabolites ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Bioactive Compounds ◽  
Entomopathogenic Fungi ◽  
Gene Clusters ◽  
Whole Genome ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters

Whole genome sequencing allows the cataloguing of the parvome (secondary metabolome) of hypocrealean entomopathogenic fungi, uncovering biosynthetic gene clusters for known and novel bioactive compounds with ecological and pharmaceutical significance.

scholarly journals Caries-Associated Biosynthetic Gene Clusters in Streptococcus mutans

2020 ◽  
Vol 99 (8) ◽  
pp. 969-976 ◽  
Author(s):  
S.S. Momeni ◽  
S.M. Beno ◽  
J.L. Baker ◽  
A. Edlund ◽  
T. Ghazal ◽  
...  
Keyword(s):  
Streptococcus Mutans ◽  
Genome Sequencing ◽  
Large Scale ◽  
Biological Activities ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Microbial Diseases ◽  
High Caries Risk

Early childhood caries (ECC) is a chronic disease affecting the oral health of children globally. This disease is multifactorial, but a primary factor is cariogenic microorganisms such as Streptococcus mutans. Biosynthetic gene clusters (BGCs) encode small molecules with diverse biological activities that influence the development of many microbial diseases, including caries. The purpose of this study was to identify BGCs in S. mutans from a high-caries risk study population using whole-genome sequencing and assess their association with ECC. Forty representative S. mutans isolates were selected for genome sequencing from a large-scale epidemiological study of oral microbiology and dental caries in children from a localized Alabama population. A total of 252 BGCs were identified using the antiSMASH BGC-mining tool. Three types of BGCs identified herein—butyrolactone-like, ladderane-like, and butyrolactone-ladderane-like hybrid (BL-BGC)—have not been reported in S. mutans. These 3 BGCs were cross-referenced against public transcriptomics data, and were found to be highly expressed in caries subjects. Furthermore, based on a polymerase chain reaction screening for core BL genes, 93% of children with BL-BGC had ECC. The role of BL-BGC was further investigated by examining cariogenic traits and strain fitness in a deletion mutant using in vitro biofilm models. Deletion of the BL-BGC significantly increased biofilm pH as compared to the parent strain, while other virulence and fitness properties remained unchanged. Intriguingly, BL-BGC containing strains produced more acid, a key cariogenic feature, and less biofilm than the model cariogenic strain S. mutans UA159, suggesting the importance of this BL-BGC in S. mutans–mediated cariogenesity. The structure of any BL-BGC derived metabolites, their functions, and mechanistic connection with acid production remain to be elucidated. Nevertheless, this study is the first to report the clinical significance of a BL-BGC in S. mutans. This study also highlights pangenomic diversity, which is likely to affect phenotype and virulence.

scholarly journals Resistance Gene-Directed Genome Mining of 50 Aspergillus species

2018 ◽  
Author(s):  
Inge Kjærbølling ◽  
Tammi Vesth ◽  
Mikael R. Andersen
Keyword(s):  
Secondary Metabolites ◽  
Resistance Gene ◽  
Genome Sequencing ◽  
Genome Mining ◽  
Gene Clusters ◽  
Rational Approach ◽  
Whole Genome ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Valuable Compounds

AbstractFungal secondary metabolites are a rich source of valuable natural products. Genome sequencing have revealed an enormous potential from predicted biosynthetic gene clusters. It is however currently a time consuming task and an unfeasible task to characterize all biosynthetic gene cluster and to identify possible uses of the compounds. A rational approach is needed to identify promising gene clusters responsible for producing valuable compounds. Several valuable bioactive clusters have been shown to include a resistance gene which is a paralog of the target gene inhibited by the compound. This mechanism can be used to design a rational approach selecting those clusters.We have developed a pipeline FRIGG (Fungal Resistance Gene-directed Genome mining) identifying putative resistance genes found in biosynthetic gene clusters based on homology patterns of the cluster genes. The FRIGG pipeline has been run using 51 Aspergillus and Penicillium genomes, identifying 72 unique protein families with putative resistance genes using various settings in the pipeline. The pipeline was also able to identify the characterized resistance gene inpE from the Fellutamide B cluster thereby validating the approach.We have successfully developed an approach identifying putative valuable bio-active clusters based on a specific resistance mechanism. This approach will be highly useful as an ever increasing amount of genomic data becomes available — the art of identifying and selecting clusters producing novel valuable compounds will only become more crucial.ImportanceSpecies belonging to the Aspergillus genus are known to produce a large number of secondary metabolites, some of these compounds are bioactive and used as pharmaceuticals such as penicillin, cyclosporin and statin. With whole genome sequencing it became apparent that the genetic potential for secondary metabolite production is much bigger than expected. As an increasing number of species are whole genome sequenced an immense number of secondary metabolite genes are predicted and the question of how to selectively identify novel bioactive compounds from this information arises. To address this question, we have created a pipeline identifying genes likely involved in the production of bioactive compounds based on a resistance gene hypothesis approach.

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.

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.

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