Biosynthetic gene clusters. Medical search. Frequent questions

We identified several SM-encoding biosynthetic gene clusters (BGCs) from the metagenomic data of lean and obese individuals and found significant association between some BGCs, including those that produce hitherto unknown SM, and obesity. (hindawi.com)
The biosynthesis of SMs is controlled by enzymes encoded by biosynthetic gene clusters (BGCs). (hindawi.com)
Most microbial BGCs that have been identified so far contain genes encoding core biosynthetic enzymes such as polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS). (hindawi.com)
By culturing microorganisms under standard laboratory conditions, most biosynthetic gene clusters (BGCs) are not expressed, and thus, the products are not produced. (dtu.dk)
To explore this biosynthetic potential, we developed a novel "semi-targeted" approach focusing on activating "silent" BGCs by concurrently introducing a group of regulator genes into streptomycetes of the Tübingen strain collection. (dtu.dk)
To explore this biosynthetic potential, we developed a novel "semi-targeted" approach focusing on activating "silent" BGCs by concurrently introducing a group of regulator genes into streptomycetes of the T{\"u}bingen strain collection. (dtu.dk)
In recent years, it has become evident that bacteria harbor a large, hidden reservoir of potential natural products in the form of silent or cryptic biosynthetic gene clusters (BGCs). (princeton.edu)
Streptomyces bacteria produce numerous specialized metabolites with industrial and medicinal applications, and they contain many associated biosynthetic gene clusters (BGCs). (mdpi.com)
Most fungal natural products are encoded in regions of the genome called biosynthetic gene clusters (BGCs). (drugdiscoverynews.com)
BGCs can contain synthase genes to help make the molecule, genes encoding transcription factors to induce its expression, and transporters to shuttle the new natural product out of the cell. (drugdiscoverynews.com)
Using genome mining, we have discovered a pair of lasso peptide biosynthetic gene clusters (BGCs) that include cytochrome P450 genes. (rsc.org)
genome revealed 19 predicted biosynthetic gene clusters (BGCs) in clovibactin, and BLASTN alignment revealed 72% identity between the clovibactin and teixobactin BGCs. (news-medical.net)
The sequencing datawill cover ~ 240 Megabases and will be assembled into contigs long enough (~ 40 Kilobases) to represent potential biosynthetic gene clusters(BGCs). (sbir.gov)
A primary purpose of the UCSF study was to identify the biosynthetic gene clusters (BGCs) that contain the genetic blueprints for creating such molecules. (drugdiscoverynews.com)
When they used this algorithm to systematically analyze genes in the human microbiome, they identified 3,000 BGCs at different body sites. (drugdiscoverynews.com)

Covington, BC, Xu, F & Seyedsayamdost, MR 2021, ' A Natural Product Chemist's Guide to Unlocking Silent Biosynthetic Gene Clusters ', Annual review of biochemistry , vol. 90, pp. 763-788. (princeton.edu)
Specifically, Dr. Zhao and colleagues, including colleagues from Singapore's Agency for Science, Technology, and Research, have been using a CRISPR/Cas9 knock-in strategy to activate silent biosynthetic gene clusters (BCGs) in bacteria. (genengnews.com)
To mine for undiscovered genomic treasure, the researchers first used computational tools to identify silent biosynthetic gene clusters-small groups of genes involved in making chemical products. (genengnews.com)
The team succeeded in activating a number of silent biosynthetic gene clusters. (genengnews.com)

BGDM Docker integrates a software for genome annotation (Prokka), a software for pan-genome analysis and classification (PanX) and a software dedicated to identify clusters of biosynthetic genes, along with the metabolites that can be produced from such clusters (anti-SMASH). (peerj.com)
A BGC is a group of genes located close together in the genome that are involved in the same metabolic pathways. (sciencedaily.com)
We are learning that the physical location of genes within the genome is important," Bryson said. (sciencedaily.com)
The tylosin-biosynthetic (tyl) gene cluster occupies about 1% of the genome of Streptomycesfradiae and includes at least 43 open reading frames. (nih.gov)

Although its basic precursors (3-amino-5-hydroxy benzoic acid AHBA, and acetic and propionic acids) had been established, and several biosynthetic intermediates had been identified, very little was known about the origin of AHBA nor had the PKS and the various genes and enzymes that modify the initial intermediate been characterized. (nih.gov)
Disruption of the PKS genes at the end of rifA abolished rifamycin B production and resulted in the formation of P8/1-OG, a known shunt product of rifamycin biosynthesis, whereas disruption of the orf6 and orf9 genes, which may encode deoxysugar biosynthesis enzymes, had no apparent effect. (nih.gov)
This study reports a 22-bp nucleotide insertion-deletion (indel) genetic polymorphism that may be causally related to the control of gene expression of the fatty acid desaturases, enzymes that control the biosynthesis of long-chain polyunsaturated fatty acids (LCPUFA) from 18-carbon PUFA. (fatsoflife.com)
Studies on polymorphisms found in one cluster of closely-located genes coding for fatty acid desaturases (FADS), enzymes that play an important role in the biosynthesis of both omega-6 and omega-3 LCPUFA, are providing an interesting perspective on the interaction between traditional diets and the population genetic history of humans. (fatsoflife.com)
None of these small polymorphisms can be clearly assigned to changes in the amino acid sequence of the FADS enzymes, and are believed to mostly influence the regulation of gene expression. (fatsoflife.com)
Therefore, many of the genes in the biosynthetic cluster encode for enzymes responsible for the synthesis of these extender units used in the hybrid synthase. (wikipedia.org)
Additionally, 193 cytochrome P450 (CYP450), 280 methyltransferase and 144 isomerase genes were identified, that are potential candidates for enzymes involved in RIN and IRN synthesis. (biomedcentral.com)
A combination of de novo transcriptome assembly and DGE analysis was shown to be a powerful method for identifying genes encoding enzymes potentially involved in the biosynthesis of important secondary metabolites in a non-model plant. (biomedcentral.com)
They also look for genes that code for enzymes like methyltransferases or dehydrogenases, which modify the natural product's molecular backbone. (drugdiscoverynews.com)
They are frequently encoded in gene clusters with lantibiotic biosynthetic enzymes and ABC transporters. (tcdb.org)
While we found non-cyanobacterial homologs of these enzymes to be rare, we identified a large number of genes encoding CylC-like enzymes in publicly available cyanobacterial genomes and in our in-house culture collection of cyanobacteria. (biomedcentral.com)
These enzymes are found in a variety of biosynthetic contexts, which include fatty-acid activating enzymes, type I or type III polyketide synthases, dialkylresorcinol-generating enzymes, monooxygenases or Rieske proteins. (biomedcentral.com)
The remarkable diversity of natural products (NPs) results from a similarly diverse pool of biosynthetic enzymes [ 2 ]. (biomedcentral.com)

The involvement of some of the genes in the biosynthesis of rifamycin B was examined. (nih.gov)
Identification of three Zwittermicin A biosynthesis-related genes from Bacillus thuringiensis subsp. (wikipedia.org)
Selected Xenorhabdus and Photorhabdus mutant strains were generated applying a chemically inducible promoter in front of the suggested fabclavine ( fcl ) biosynthesis gene cluster (BGC), followed by the analysis of the occurring fabclavines. (beilstein-journals.org)
They named the cluster oleABCD (for olefin biosynthesis), and the role of oleA in the pathway was proposed (Fig 15). (kenyon.edu)
The genes in these groups contribute to the biosynthesis of a specific natural product. (drugdiscoverynews.com)
Such bioactive compounds are found at low concentration in their natural sources, so that dissecting their biosynthetic pathways is of value for their production through heterologous biosynthesis in engineered prokaryotic microbes and fungi, such as E. coli and yeast. (biomedcentral.com)
MOCS1 gene mutations cause type A, MOCS2 gene mutations cause type B, and GPHN gene mutations cause type C. The proteins produced from each of these genes are involved in the formation (biosynthesis) of a molecule called molybdenum cofactor. (medlineplus.gov)
Mutations in the MOCS1 , MOCS2 , or GPHN gene reduce or eliminate the function of the associated protein, which impairs molybdenum cofactor biosynthesis. (medlineplus.gov)

The molecule is also of interest from a metabolic perspective because it represents a new structural class of antibiotic and suggests a crossover between polyketide and non-ribosomal peptide biosynthetic pathways. (wikipedia.org)
The biosynthetic pathways of RIN and IRN are largely unknown. (biomedcentral.com)
The BGC cluster of the beautyberry plant contains genes that encode two distinct terpenoid pathways. (sciencedaily.com)
Gene expression data were normalized with DESeq2 [40], and PAL values were calculated for gene-centric pathways using R [41] . (researchgate.net)
Here, we used the human interactome model to algorithmically build 7470 molecular pathways centered around individual gene products. (researchgate.net)
We assessed their associations with tumor type and survival in comparison with the previous generation of molecular pathway biomarkers (3022 "classical" pathways) and with the RNA transcripts or proteomic profiles of individual genes, for 8141 and 1117 samples, respectively. (researchgate.net)
For all analytes in RNA and proteomic data, respectively, we found a total of 7441 and 7343 potential biomarker associations for gene-centric pathways, 3020 and 2950 for classical pathways, and 24,349 and 6742 for individual genes. (researchgate.net)
The discovery of these biosynthetic pathways relies on the genomic and transcriptomic, metabolomic information. (biomedcentral.com)

2016) DNA affinity capturing identifies new regulators of the heterologously expressed novobiocin gene cluster in Streptomyces coelicolor M512. (uni-tuebingen.de)
Saleh O, Flinspach K, Westrich L, Kulik A, Gust B , Fiedler HP, Heide L. (2012) Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663. (uni-tuebingen.de)
2011) The actinobacteria-specific gene wblA controls major developmental transitions in Streptomyces coelicolor A3(2). (uni-tuebingen.de)
Details of this work appeared April 10 in the journal Nature Chemical Biology, in an article entitled, "CRISPR-Cas9 Strategy for Activation of Silent Streptomyces Biosynthetic Gene Clusters. (genengnews.com)
In the past, it was very difficult to turn on or off a specific gene in Streptomyces species. (genengnews.com)
As a demonstration, the researchers isolated and determined the structure of one of the novel compounds produced from a silent biosynthetic gene cluster and found that it has a fundamentally different structure from other Streptomyces -derived drugs-a potential diamond in the rough. (genengnews.com)

2013) Phage p1-derived artificial chromosomes facilitate heterologous expression of the FK506 gene cluster. (uni-tuebingen.de)
Our research program targets the development of the next-generation natural compound production technology which leads the production of novel compounds by heterologous expression system applying on cryptic biosynthetic genes. (go.jp)

This knowledge meant the scientists could focus on searching for certain types of gene clusters in samples rather than having to sequence and analyse the whole genomes of bacteria. (eurekalert.org)

Furthermore, sequence homology between mammalian and fungal genes in the GPI pathway show modest conservation raising the chances of finding fungal-selective molecules with good therapeutic index 8 . (nature.com)
Based on mutant studies, the biosynthetic cluster involved in zwittermicin production has been identified and the pathway has been proposed. (wikipedia.org)
370 15.3.3 A¯atoxin Biosynthetic Pathway. (taylorfrancis.com)
372 15.3.5 A¯atoxin Biosynthetic Pathway Gene Cluster. (taylorfrancis.com)
Individual gene expression and molecular pathway activation profiles were shown to be effective biomarkers in many cancers. (researchgate.net)
The red region indicates the carbon to carbon bond created by the head-to-head biosynthetic pathway (Picture from Sukovich et al. (kenyon.edu)
Head-to-head biosynthetic pathway used to produce hydrocarbons. (kenyon.edu)

To investigate adaptive evolution of FHB pathogens, we performed population-level analyses to characterize genomic structure, signatures of natural selection, and differences in gene content among isolates. (usda.gov)
However, functional annotation of population-differentiating genomic regions revealed numerous genes involved in host invasion, toxin production, and secondary metabolism, and implicated plant hosts, microbial competitors, and temperature and light as major drivers of adaptive divergence. (usda.gov)

This genetic variant, termed an indel (insertion/deletion mutation), was found to influence the regulation of the expression levels of both FADS-1 and FADS-2 in a cellular system, with the minor allele in Japanese people being associated with lower expression of the FADS-1 and FADS-2 genes. (fatsoflife.com)
Evolution of genetic architecture and gene regulation in biphenyl/PCB-degrading bacteria. (go.jp)

At least five genes were shown to be essential for the synthesis of AHBA, five genes were determined to encode the modular type I PKS that uses AHBA as the starter unit, and 20 or more genes appear to govern modification of the polyketide-derived framework, and rifamycin resistance and export. (nih.gov)

Scientists have previously identified clusters of bacterial genes that are particularly good at producing therapeutics. (eurekalert.org)

A set of 34 genes clustered around the rifK gene encoding AHBA synthase were defined by sequencing all but 5 kilobases (kb) of a 95 kb contiguous region of DNA from A. mediterranei. (nih.gov)
The genes responsible for the production of zwittermicin A are located on a 16 kb cluster containing nine orfs and a self resistant gene zmaR, a gene that encodes an acylation enzyme that deactivate zwittermicin A. The hybrid synthase used in zwittermicin A production utilizes modified extender units such as hydroxymalonyl-ACP, aminomalonyl-ACP and 2,3-diaminopropionate. (wikipedia.org)
Genes encoding for the seven component hybrid synthase responsible for the assembly of the backbone is likely located on the largest gene, orf8. (wikipedia.org)

Homologs of CylC are also found in other characterized cyanobacterial secondary metabolite biosynthetic gene clusters. (biomedcentral.com)

Based on the historical success of natural products as therapeutics, biosynthetic dark matter is likely to hold enormous potential for biomedicine," says Dr Brady. (eurekalert.org)

A specific sequence of mutations triggers with the APC gene following with mutations in the KRAS, TP53, and DCC genes are observed in approximately 70% of CRC cases ( Fearon and Vogelstein, 1990 ). (frontiersin.org)
Then they used CRISPR technology to insert a strong promoter sequence before each gene that they wanted to activate, prompting the cell to make the natural products that the genes clusters coded for. (genengnews.com)

Here, we use a reporter gene-based screen in Saccharomyces cerevisiae for the discovery of antifungal inhibitors of GPI-anchoring of proteins, and identify the oligocyclopropyl-containing natural product jawsamycin (FR-900848) as a potent hit. (nature.com)

The vast majority of biosynthetic gene clusters are not expressed under laboratory conditions, or are expressed at very low levels. (genengnews.com)

Joshua Herbeck: Are HIV genetic clusters enriched with transmitters? (birs.ca)

Putative regulatory genes were also identified. (nih.gov)
Rifamycin production in A. mediterranei is governed by a single gene cluster consisting of structural, resistance and export, and regulatory genes. (nih.gov)
In addition to structural genes required for tylosin production, the tyl cluster contains three resistance determinants and several regulatory genes. (nih.gov)

Genes encoding CylC homologs are widely distributed throughout the cyanobacterial tree of life, within biosynthetic gene clusters of distinct architectures (combination of unique gene groups). (biomedcentral.com)

The penultimate column indicates which strains had mutations in the O1-antigen biosynthetic complex and in other genes in the chromosome, with the mutated gene designated. (cdc.gov)
Sporadics are heterogeneous, and different genes undergo point mutations. (frontiersin.org)
Two well-known examples for polyposis and HNPCC are familial adenomatous polyposis (FAP) and Lynch syndrome, respectively, in which occurs as a result of mutations in DNA repair genes ( Lynch and de la Chapelle, 2003 ). (frontiersin.org)
Molybdenum cofactor deficiency is caused by mutations in the MOCS1 , MOCS2 , or GPHN gene. (medlineplus.gov)
which means both copies of the gene in each cell have mutations. (medlineplus.gov)

But Dr. Zhao's team reports that they have now uncovered even more potential treasure formerly hidden in silent genes. (genengnews.com)
The study of the "biosynthetic" content of these soils shows their potential for drug discovery. (eurekalert.org)
Researchers created a machine-learning algorithm that enabled a computer to identify known genes that produce small molecules with potential as drugs. (drugdiscoverynews.com)

In 2012, a much larger, 22-base pair long stretch of nucleotides was identified within a part of the FADS-2 gene that is not translated to protein (an intron). (fatsoflife.com)

Positive Selection of an Indel Polymorphism in the FADS Gene Cluster May be Driving Long-Chain PUFA Biosynthetic Capacity in Specific Human Populations. (fatsoflife.com)
The three populations differed in gene content, with 134 genes showing population-specific patterns of conservation. (usda.gov)

TÜ17 activated the production of mayamycin A. By using the individual regulator genes, we proved that Aur1P, was responsible for the activation. (dtu.dk)
T{\"U}17 activated the production of mayamycin A. By using the individual regulator genes, we proved that Aur1P, was responsible for the activation. (dtu.dk)

Essentially, the scientists turned on unexpressed, or "silent," gene clusters in a common class of bacteria that naturally produce many compounds already used as antibiotics, anticancer agents, and other drugs. (genengnews.com)

The analysis revealed soils particularly rich in important gene clusters. (eurekalert.org)

The scientists were also able to identify hotspots for 'biosynthetic dark matter' - gene clusters new to science. (eurekalert.org)
Using mutagenesis experiments, scientists discovered that the oleA gene product catalyzed head-to-head condensation (Picture from Sukovich et al. (kenyon.edu)
The scientists also used mutgenesis experiments to identify the gene cluster responsible for the olefin production. (kenyon.edu)

The strongest signals of selective sweeps were observed at the trichothecene biosynthetic gene cluster. (usda.gov)

Novotna J, Gust B , Kulik A, Spizek J, Heide L. (2013) Five gene products are required for assembly of the central pyrrole moiety of coumermycin A(1). (uni-tuebingen.de)

Energetic digging sounds can be heard from the direction of the University of Illinois at Urbana-Champaign, where a research team led by chemical and biomolecular engineering professor Huimin Zhao, Ph.D., has been using a CRISPR/Cas9 gene-editing technology to look for new drug candidates. (genengnews.com)

For example, in a hot spring sample from New Mexico, they found clusters similar to those that produce epoxamicin. (eurekalert.org)
In samples from Brazil, they found genes that may be able to make new versions of bleomycin, an anticancer agent listed on the World Health Organisation's list of essential medicines. (eurekalert.org)

The oleA gene is part of the gene cluster required for shewanella to produce hydrocarbons. (kenyon.edu)

In addition to specialized metabolite genes, we show that the ArcZ regulon affects approximately 15% of all transcripts in Photorhabdus and Xenorhabdus . (nature.com)

These genes are like the individual pearls on a necklace -- separate and yet connected. (sciencedaily.com)
An affected individual usually inherits one altered copy of the gene from each parent. (medlineplus.gov)
At least one individual with molybdenum cofactor deficiency inherited two mutated copies of the MOCS1 gene through a mechanism called uniparental isodisomy. (medlineplus.gov)

Anatomy3

Organisms45

Diseases1

Chemicals and Drugs116

Analytical, Diagnostic and Therapeutic Techniques and Equipment27

Phenomena and Processes60

Disciplines and Occupations2

Technology, Industry, Agriculture4

Information Science4

Health Care1

BGCs15

Silent biosynthetic gene clusters4

Genome4

Enzymes13

Biosynthesis8

Pathways8

Streptomyces6

Heterologous Expression2

Genomes1

Pathway7

Genomic2

Regulation2

Encode1

Bacterial genes1

Synthase3

Secondary1

Therapeutics1

Sequence2

Proteins1

Laboratory conditions1

Genetic1

Regulatory3

Distinct1

Mutations5

Potential3

Protein1

Populations2

Activation2

Bacteria1

Analysis1

Scientists3

Selective1

Products1

Candidates1

Found2

Produce1

Addition1

Individual3