scholarly journals Salicylic Acid Biosynthesis and Metabolism: A Divergent Pathway for Plants and Bacteria

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 705
Author(s):  
Awdhesh Kumar Mishra ◽  
Kwang-Hyun Baek
Keyword(s):  
Salicylic Acid ◽  
Bacterial Species ◽  
Shikimate Pathway ◽  
Gene Clusters ◽  
Defense Responses ◽  
Biosynthetic Gene ◽  
Biosynthetic Enzyme ◽  
Biosynthetic Gene Clusters ◽  
Acid Biosynthesis ◽  
Common Precursor

Salicylic acid (SA) is an active secondary metabolite that occurs in bacteria, fungi, and plants. SA and its derivatives (collectively called salicylates) are synthesized from chorismate (derived from shikimate pathway). SA is considered an important phytohormone that regulates various aspects of plant growth, environmental stress, and defense responses against pathogens. Besides plants, a large number of bacterial species, such as Pseudomonas, Bacillus, Azospirillum, Salmonella, Achromobacter, Vibrio, Yersinia, and Mycobacteria, have been reported to synthesize salicylates through the NRPS/PKS biosynthetic gene clusters. This bacterial salicylate production is often linked to the biosynthesis of small ferric-ion-chelating molecules, salicyl-derived siderophores (known as catecholate) under iron-limited conditions. Although bacteria possess entirely different biosynthetic pathways from plants, they share one common biosynthetic enzyme, isochorismate synthase, which converts chorismate to isochorismate, a common precursor for synthesizing SA. Additionally, SA in plants and bacteria can undergo several modifications to carry out their specific functions. In this review, we will systematically focus on the plant and bacterial salicylate biosynthesis and its metabolism.

scholarly journals Understanding the evolutionary origins of bacterial natural products with immunosuppressant properties

2019 ◽  
Author(s):  
Wenfa Ng
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Human Body ◽  
Immune Cells ◽  
Bacterial Species ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Drug Candidates

Actinobacteria and streptomyces are known to produce a variety of natural products, some of which confer antibiotic or immunosuppressive activities. While it is understandable that microbes develop the ability to synthesize molecules such as antibiotics that attack other competing microbes, but why would a secondary metabolite (natural product) synthesized by a microbe confer immunosuppressive activities? Was the capability to synthesize such a molecule endowed by evolution in the context of enabling microbes to develop resistance to immune cells of the human body? Or did the capability come from the need to colonize human body surfaces or gut to gain a survival niche for the microbe? Given that actinobacteria and streptomyces are soil microbes not usually associated with human body surfaces, could their biosynthetic capability for particular immunosuppressants arise from horizontal gene transfer from bacteria that colonize human body surfaces and subsequently develop the ability to synthesize the pertinent compounds through evolution? An alternate line of thinking on this issue touches on the possibility that microbes could encounter analogs of immuno-active molecules in their natural environment. Such molecules might elicit undesired physiological effects on the microbes, which place a selection pressure on microbes to develop countermeasures to the immuno-active molecules through mutations. Hence, through evolution, microbes could have developed the capability to synthesize secondary metabolites able to bind analogs of immuno-active molecules and help sequester them or quench their bioactivity. Subsequent profiling of such secondary metabolites in drug discovery efforts could have uncovered compounds with immunosuppressant activity which are originally developed for counteracting analogs of immuno-active molecules in the environment. It has to be recognized that analogs of immuno-active compounds remain somewhat dissimilar to immune compounds secreted by human immune cells, but they likely share common motifs for protein-secondary metabolite interactions. Direct evidence of the evolution of natural products with immunosuppressant activities could only be obtained from challenging suitable bacterial species with immuno-active molecules. Long cultivation experiments with multiple generations may result in the evolution of biosynthetic gene clusters for the synthesis of natural products able to sequester or quench immuno-active molecules. But, on the another hand, understanding relative binding affinities between a library of natural products and immuno-active molecules from humans would suggest drug candidates and their biosynthetic gene clusters. Subsequent phylogenetic analysis of cluster genes with their homologs from other species may yield insights into the evolution of genes and their putative function.

scholarly journals Understanding the evolutionary origins of bacterial natural products with immunosuppressant properties

2019 ◽  
Author(s):  
Wenfa Ng
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Human Body ◽  
Immune Cells ◽  
Bacterial Species ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Drug Candidates

Actinobacteria and streptomyces are known to produce a variety of natural products, some of which confer antibiotic or immunosuppressive activities. While it is understandable that microbes develop the ability to synthesize molecules such as antibiotics that attack other competing microbes, but why would a secondary metabolite (natural product) synthesized by a microbe confer immunosuppressive activities? Was the capability to synthesize such a molecule endowed by evolution in the context of enabling microbes to develop resistance to immune cells of the human body? Or did the capability come from the need to colonize human body surfaces or gut to gain a survival niche for the microbe? Given that actinobacteria and streptomyces are soil microbes not usually associated with human body surfaces, could their biosynthetic capability for particular immunosuppressants arise from horizontal gene transfer from bacteria that colonize human body surfaces and subsequently develop the ability to synthesize the pertinent compounds through evolution? An alternate line of thinking on this issue touches on the possibility that microbes could encounter analogs of immuno-active molecules in their natural environment. Such molecules might elicit undesired physiological effects on the microbes, which place a selection pressure on microbes to develop countermeasures to the immuno-active molecules through mutations. Hence, through evolution, microbes could have developed the capability to synthesize secondary metabolites able to bind analogs of immuno-active molecules and help sequester them or quench their bioactivity. Subsequent profiling of such secondary metabolites in drug discovery efforts could have uncovered compounds with immunosuppressant activity which are originally developed for counteracting analogs of immuno-active molecules in the environment. It has to be recognized that analogs of immuno-active compounds remain somewhat dissimilar to immune compounds secreted by human immune cells, but they likely share common motifs for protein-secondary metabolite interactions. Direct evidence of the evolution of natural products with immunosuppressant activities could only be obtained from challenging suitable bacterial species with immuno-active molecules. Long cultivation experiments with multiple generations may result in the evolution of biosynthetic gene clusters for the synthesis of natural products able to sequester or quench immuno-active molecules. But, on the another hand, understanding relative binding affinities between a library of natural products and immuno-active molecules from humans would suggest drug candidates and their biosynthetic gene clusters. Subsequent phylogenetic analysis of cluster genes with their homologs from other species may yield insights into the evolution of genes and their putative function.

scholarly journals A widely distributed genus of soil Acidobacteria genomically enriched in biosynthetic gene clusters

2021 ◽  
Author(s):  
Alexander Crits-Christoph ◽  
Spencer Diamond ◽  
Basem Al-Shayeb ◽  
Luis Valentin-Alvarado ◽  
Jillian F Banfield
Keyword(s):  
Novel Species ◽  
Bacterial Species ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Metabolic Diversity ◽  
Biosynthetic Gene Clusters ◽  
Specialized Metabolites ◽  
Soil Ecosystems ◽  
High Degree

Bacteria of the phylum Acidobacteria are one of the most abundant bacterial across soil ecosystems, yet they are represented by comparatively few sequenced genomes, leaving gaps in our understanding of their metabolic diversity. Recently, genomes of Acidobacteria species with unusually large repertoires of biosynthetic gene clusters (BGCs) were reconstructed from grassland soil metagenomes, but the degree to which these species are widespread is still unknown. To investigate this, we augmented a dataset of publicly available Acidobacteria genomes with 46 metagenome-assembled genomes recovered from permanently saturated organic-rich soils of a vernal (spring) pool ecosystem in Northern California. We recovered high quality genomes for three novel species from Candidatus Angelobacter (a proposed subdivision 1 Acidobacterial genus), a genus that is genomically enriched in genes for specialized metabolite biosynthesis. Acidobacteria were particularly abundant in the vernal pool sediments, and a Ca. Angelobacter species was the most abundant bacterial species detected in some samples. We identified numerous diverse biosynthetic gene clusters in these genomes, and also in additional genomes from other publicly available soil metagenomes for other related Ca. Angelobacter species. Metabolic analysis indicates that Ca. Angelobacter likely are aerobes that ferment organic carbon, with potential to contribute to carbon compound turnover in soils. Using metatranscriptomics, we identified in situ expression of specialized metabolic traits for two species from this genus. In conclusion, we expand genomic sampling of the uncultivated Ca. Angelobacter, and show that they represent common and sometimes highly abundant members of dry and saturated soil communities, with a high degree of capacity for synthesis of diverse specialized metabolites.

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.

Sign in / Sign up

Export Citation Format

Share Document