scholarly journals Tracking Down Biotransformation to the Genetic Level: Identification of a Highly Flexible Glycosyltransferase from Saccharothrix espanaensis

2013 ◽  
Vol 79 (17) ◽  
pp. 5224-5232 ◽  
Author(s):  
Tina Strobel ◽  
Yvonne Schmidt ◽  
Anton Linnenbrink ◽  
Andriy Luzhetskyy ◽  
Marta Luzhetska ◽  
...  
Keyword(s):  
Natural Products ◽  
Phenolic Compounds ◽  
Natural Product ◽  
Defense Mechanism ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Gene Encoding ◽  
Content Type ◽  
Genetic Level ◽  
Level Identification

ABSTRACTSaccharothrix espanaensisis a member of the orderActinomycetales. The genome of the strain has been sequenced recently, revealing 106 glycosyltransferase genes. In this paper, we report the detection of a glycosyltransferase fromSaccharothrix espanaensiswhich is able to rhamnosylate different phenolic compounds targeting different positions of the molecules. The gene encoding the flexible glycosyltransferase is not located close to a natural product biosynthetic gene cluster. Therefore, the native function of this enzyme might be not the biosynthesis of a secondary metabolite but the glycosylation of internal and external natural products as part of a defense mechanism.

scholarly journals mSphere of Influence: Synthetic Biology of Natural Product Biosynthesis

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Mark C. Walker
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Natural Product ◽  
Gene Cluster ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Natural Product Biosynthesis ◽  
Antibiotic Compounds ◽  
Approaches To Study

ABSTRACT Mark Walker studies the biosynthesis and engineering of bacterial natural products with the long-term goal of identifying new antibiotic compounds. In this mSphere of Influence, he reflects on how “Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A” by K. Yamanaka, K. A. Reynolds, R. D. Kersten, K. S. Ryan, et al. (Proc Natl Acad Sci USA 111:1957–1962, 2014, https://doi.org/10.1073/pnas.1319584111) impacted his thinking on using synthetic biology approaches to study natural product biosynthesis.

scholarly journals Natural Product Gene Clusters in the Filamentous Nostocales Cyanobacterium HT-58-2

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 356
Author(s):  
Xiaohe Jin ◽  
Eric S. Miller ◽  
Jonathan S. Lindsey
Keyword(s):  
Natural Products ◽  
Nitrogen Fixation ◽  
Natural Product ◽  
Microbial Consortium ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Nitrogen Stress ◽  
Biosynthetic Gene ◽  
Tetrapyrrole Biosynthesis ◽  
The Rich

Cyanobacteria are known as rich repositories of natural products. One cyanobacterial-microbial consortium (isolate HT-58-2) is known to produce two fundamentally new classes of natural products: the tetrapyrrole pigments tolyporphins A–R, and the diterpenoid compounds tolypodiol, 6-deoxytolypodiol, and 11-hydroxytolypodiol. The genome (7.85 Mbp) of the Nostocales cyanobacterium HT-58-2 was annotated previously for tetrapyrrole biosynthesis genes, which led to the identification of a putative biosynthetic gene cluster (BGC) for tolyporphins. Here, bioinformatics tools have been employed to annotate the genome more broadly in an effort to identify pathways for the biosynthesis of tolypodiols as well as other natural products. A putative BGC (15 genes) for tolypodiols has been identified. Four BGCs have been identified for the biosynthesis of other natural products. Two BGCs related to nitrogen fixation may be relevant, given the association of nitrogen stress with production of tolyporphins. The results point to the rich biosynthetic capacity of the HT-58-2 cyanobacterium beyond the production of tolyporphins and tolypodiols.

scholarly journals Shared PKS modules in biosynthesis of synergistic laxaphycins

2020 ◽  
Author(s):  
LMP Heinilä ◽  
DP Fewer ◽  
J Jokela ◽  
M Wahlsten ◽  
A Jortikka ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Polyketide Synthase ◽  
Biosynthetic Gene Cluster ◽  
Future Research ◽  
Biosynthetic Pathways ◽  
Biosynthetic Gene ◽  
Wide Range ◽  
Peptide Synthetase ◽  
Antiproliferative Activities

AbstractCyanobacteria produce a wide range of lipopeptides that exhibit potent membrane-disrupting activities. Laxaphycins consist of two families of structurally distinct macrocyclic lipopeptides that act in a synergistic manner to produce antifungal and antiproliferative activities. Laxaphycins are produced by range of cyanobacteria but their biosynthetic origins remain unclear. Here, we identified the biosynthetic pathways responsible for the biosynthesis of the laxaphycins produced by Scytonema hofmannii PCC 7110. We show that these laxaphycins, called scytocyclamides, are produced by this cyanobacterium and are encoded in a single biosynthetic gene cluster with shared polyketide synthase enzymes initiating two distinct non-ribosomal peptide synthetase pathways. To our knowledge, laxaphycins are the first clearly distinct polyketide synthase and non-ribosomal peptide synthetase hybrid natural products with shared branched biosynthesis. The unusual mechanism of shared enzymes synthesizing two distinct types of products may aid future research in identifying and expressing natural product biosynthetic pathways and in expanding the known biosynthetic logic of this important family of natural products.

scholarly journals Mining metagenomes for natural product biosynthetic gene clusters: unlocking new potential with ultrafast techniques

2021 ◽  
Author(s):  
Emiliano Pereira-Flores ◽  
Marnix Medema ◽  
Pier Luigi Buttigieg ◽  
Peter Meinicke ◽  
Frank Oliver Glöckner ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Human Microbiome ◽  
Gene Clusters ◽  
Human Microbiome Project ◽  
Biosynthetic Gene Cluster ◽  
Metagenomic Data ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Wide Range

Microorganisms produce an immense variety of natural products through the expression of Biosynthetic Gene Clusters (BGCs): physically clustered genes that encode the enzymes of a specialized metabolic pathway. These natural products cover a wide range of chemical classes (e.g., aminoglycosides, lantibiotics, nonribosomal peptides, oligosaccharides, polyketides, terpenes) that are highly valuable for industrial and medical applications1. Metagenomics, as a culture-independent approach, has greatly enhanced our ability to survey the functional potential of microorganisms and is growing in popularity for the mining of BGCs. However, to effectively exploit metagenomic data to this end, it will be crucial to more efficiently identify these genomic elements in highly complex and ever-increasing volumes of data2. Here, we address this challenge by developing the ultrafast Biosynthetic Gene cluster MEtagenomic eXploration toolbox (BiG-MEx). BiG-MEx rapidly identifies a broad range of BGC protein domains, assess their diversity and novelty, and predicts the abundance profile of natural product BGC classes in metagenomic data. We show the advantages of BiG-MEx compared to standard BGC-mining approaches, and use it to explore the BGC domain and class composition of samples in the TARA Oceans3 and Human Microbiome Project datasets4. In these analyses, we demonstrate BiG-MEx’s applicability to study the distribution, diversity, and ecological roles of BGCs in metagenomic data, and guide the exploration of natural products with clinical applications.

scholarly journals Antibiotic Resistance Mechanisms Inform Discovery: Identification and Characterization of a Novel Amycolatopsis Strain Producing Ristocetin

2014 ◽  
Vol 58 (10) ◽  
pp. 5687-5695 ◽  
Author(s):  
Andrew W. Truman ◽  
Min Jung Kwun ◽  
Jinhua Cheng ◽  
Seung Hwan Yang ◽  
Joo-Won Suh ◽  
...  
Keyword(s):  
Cell Wall ◽  
Antibiotic Resistance ◽  
Natural Product ◽  
Gene Cluster ◽  
Wall Stress ◽  
Biosynthetic Gene Cluster ◽  
Resistance Mechanisms ◽  
Biosynthetic Gene ◽  
Single Strain ◽  
Content Type

ABSTRACTDiscovering new antibiotics is a major scientific challenge, made increasingly urgent by the continued development of resistance in bacterial pathogens. A fundamental understanding of the mechanisms of bacterial antibiotic resistance will be vital for the future discovery or design of new, more effective antibiotics. We have exploited our intimate knowledge of the molecular mechanism of glycopeptide antibiotic resistance in the harmless bacteriumStreptomyces coelicolorto develop a new two-step cell wall bioactivity screen, which efficiently identified a new actinomycete strain containing a previously uncharacterized glycopeptide biosynthetic gene cluster. The screen first identifies natural product extracts capable of triggering a generalized cell wall stress response and then specifically selects for glycopeptide antibacterials by assaying for the induction of glycopeptide resistance genes. In this study, we established a diverse natural product extract library from actinomycete strains isolated from locations with widely varying climates and ecologies, and we screened them using the novel two-step bioassay system. The bioassay ultimately identified a single strain harboring the previously unidentified biosynthetic gene cluster for the glycopeptide ristocetin, providing a proof of principle for the effectiveness of the screen. This is the first report of the ristocetin biosynthetic gene cluster, which is predicted to include some interesting and previously uncharacterized enzymes. By focusing on screening libraries of microbial extracts, this strategy provides the certainty that identified producer strains are competent for growth and biosynthesis of the detected glycopeptide under laboratory conditions.

scholarly journals New Insights into the Genetic Organization of the FK228 Biosynthetic Gene Cluster inChromobacterium violaceumNo. 968

2010 ◽  
Vol 77 (4) ◽  
pp. 1508-1511 ◽  
Author(s):  
Vishwakanth Y. Potharla ◽  
Shane R. Wesener ◽  
Yi-Qiang Cheng
Keyword(s):  
Natural Product ◽  
Gene Cluster ◽  
Gene Deletion ◽  
Regulatory Gene ◽  
Biosynthetic Gene Cluster ◽  
Transcriptional Analysis ◽  
Biosynthetic Gene ◽  
Genetic Organization

ABSTRACTThe biosynthetic gene cluster of FK228, an FDA-approved anticancer natural product, was identified and sequenced previously. The genetic organization of this gene cluster has now been delineated through systematic gene deletion and transcriptional analysis. As a result, the gene cluster is redefined to contain 12 genes:depAthroughdepJ,depM, and a newly identified pathway regulatory gene,depR.

scholarly journals Transcriptional Regulator PhlH Modulates 2,4-Diacetylphloroglucinol Biosynthesis in Response to the Biosynthetic Intermediate and End Product

2017 ◽  
Vol 83 (21) ◽  
Author(s):  
Xu Yan ◽  
Rui Yang ◽  
Rui-Xue Zhao ◽  
Jian-Ting Han ◽  
Wen-Juan Jia ◽  
...  
Keyword(s):  
Pseudomonas Fluorescens ◽  
Gene Cluster ◽  
Plant Pathogens ◽  
Feedback Regulation ◽  
Biosynthetic Gene Cluster ◽  
Sequence Motif ◽  
Target Sequence ◽  
Gene Encoding ◽  
Negative Feedback Regulation ◽  
Content Type

ABSTRACT Certain strains of biocontrol bacterium Pseudomonas fluorescens produce the secondary metabolite 2,4-diacetylphloroglucinol (2,4-DAPG) to antagonize soilborne phytopathogens in the rhizosphere. The gene cluster responsible for the biosynthesis of 2,4-DAPG is named phlACBDEFGH and it is still unclear how the pathway-specific regulator phlH within this gene cluster regulates the metabolism of 2,4-DAPG. Here, we found that PhlH in Pseudomonas fluorescens strain 2P24 represses the expression of the phlG gene encoding the 2,4-DAPG hydrolase by binding to a sequence motif overlapping with the −35 site recognized by σ70 factors. Through biochemical screening of PhlH ligands we identified the end product 2,4-DAPG and its biosynthetic intermediate monoacetylphloroglucinol (MAPG), which can act as signaling molecules to modulate the binding of PhlH to the target sequence and activate the expression of phlG. Comparison of 2,4-DAPG production between the ΔphlH, ΔphlG, and ΔphlHG mutants confirmed that phlH and phlG impose negative feedback regulation over 2,4-DAPG biosynthesis. It was further demonstrated that the 2,4-DAPG degradation catalyzed by PhlG plays an insignificant role in 2,4-DAPG tolerance but contributes to bacterial growth advantages under carbon/nitrogen starvation conditions. Taken together, our data suggest that by monitoring and down-tuning in situ levels of 2,4-DAPG, the phlHG genes could dynamically modulate the metabolic loads attributed to 2,4-DAPG production and potentially contribute to rhizosphere adaptation. IMPORTANCE 2,4-DAPG, which is synthesized by biocontrol pseudomonad bacteria, is a broad-spectrum antibiotic against bacteria, fungi, oomycetes, and nematodes and plays an important role in suppressing soilborne plant pathogens. Although most of the genes in the 2,4-DAPG biosynthetic gene cluster (phl) have been characterized, it is still not clear how the pathway-specific regulator phlH is involved in 2,4-DAPG metabolism. This work revealed the role of PhlH in modulating 2,4-DAPG levels by controlling the expression of 2,4-DAPG hydrolase PhlG in response to 2,4-DAPG and MAPG. Since 2,4-DAPG biosynthesis imposes a metabolic burden on biocontrol pseudomonads, it is expected that the fine regulation of phlG by PhlH offers a way to dynamically modulate the metabolic loads attributed to 2,4-DAPG production.

scholarly journals Composite Long- and Short-Read Sequencing Delivers a Complete Genome Sequence of B04Sm5, a Reutericyclin- and Mutanocyclin-Producing Strain of Streptococcus mutans

2020 ◽  
Vol 9 (47) ◽  
Author(s):  
Jonathon L. Baker ◽  
Anna Edlund
Keyword(s):  
Streptococcus Mutans ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Biosynthetic Gene Cluster ◽  
Commensal Bacteria ◽  
Biosynthetic Gene ◽  
Tetramic Acid ◽  
Content Type ◽  
Short Read Sequencing

ABSTRACT Streptococcus mutans strain B04Sm5 was recently shown to inhibit the growth of neighboring commensal bacteria using reutericyclin, an acylated tetramic acid produced by the muc biosynthetic gene cluster. Here, a complete genome sequence of B04Sm5 is reported.

scholarly journals Toward Biosynthetic Design and Implementation of Escherichia coli-Derived Paclitaxel and Other Heterologous Polyisoprene Compounds

2012 ◽  
Vol 78 (8) ◽  
pp. 2497-2504 ◽  
Author(s):  
Ming Jiang ◽  
Gregory Stephanopoulos ◽  
Blaine A. Pfeifer
Keyword(s):  
Escherichia Coli ◽  
Natural Products ◽  
Natural Product ◽  
Cellular Metabolism ◽  
Compound Formation ◽  
Natural Product Biosynthesis ◽  
Content Type ◽  
E Coli ◽  
Design And Implementation ◽  
Final Compound

ABSTRACTEscherichia colioffers unparalleled engineering capacity in the context of heterologous natural product biosynthesis. However, as with other heterologous hosts, cellular metabolism must be designed or redesigned to support final compound formation. This task is at once complicated and aided by the fact that the cell does not natively produce an abundance of natural products. As a result, the metabolic engineer avoids complicated interactions with native pathways closely associated with the outcome of interest, but this convenience is tempered by the need to implement the required metabolism to allow functional biosynthesis. This review focuses on engineeringE. colifor the purpose of polyisoprene formation, as it is related to isoprenoid compounds currently being pursued through a heterologous approach. In particular, the review features the compound paclitaxel and early efforts to design and overproduce intermediates throughE. coli.

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