• Compound (1), ilicicolinic acid B, was found to be produced from polyketide synthase (PKS) StBA and that AscCABD are responsible for the biosynthesis of ilicicolin A (3). (wikipedia.org)
  • Ilicicolin B (2) was found to be produced by expressing AscC (polyketide synthase) which is then followed by expression of AscA (prenyltransferase). (wikipedia.org)
  • Indanomycin is biosynthesized by a hybrid nonribosomal peptide synthase/polyketide synthase (NRPS/PKS) followed by a number of `tailoring' steps to form the two ring systems that are present in the mature product. (iucr.org)
  • Our current focus is on understanding the structure and mechanism of this polyketide synthase. (stanford.edu)
  • In this study, we elucidated the biosynthetic pathway encoded by , a hybrid polyketide synthase and nonribosomal peptide synthetase (PKS/NRPS) biosynthetic gene cluster (BGC), present in a number of globally distributed strains. (jcvi.org)
  • The mupirocin trans-AT polyketide synthase pathway, provides a model system for manipulation of antibiotic biosynthesis. (birmingham.ac.uk)
  • Gene deletion and heterologous expression proved that the phenethyl core structure is assembled by a polyketide synthase (UttA) harboring a methyltransferase domain. (uni-marburg.de)
  • This study provides an enzyme with a high substrate promiscuity from the less explored prenyltransferase group in cyclodipeptide synthase-related pathways. (uni-marburg.de)
  • The majority of our projects focus on biosynthetic pathways that include enzymes belonging to the polyketide synthase (PKS) class. (dtu.dk)
  • Accumulation of the polyketide aglycone is controlled by glycosylated macrolides and optimal performance of the complex polyketide synthase enzyme requires the activity of an editing thioesterase. (nih.gov)
  • Several classes of structurally diverse secondary metabolites with a broad spectrum of bioactivities (e.g. antibacterial, insecticidal, antifungal) are known from different Xenorhabdus and Photorhabdus strains and are produced by nonribosomal peptide synthetases (NRPS) and the fatty acid synthase (FAS)-related polyketide synthases (PKS) or even hybrids thereof. (uni-frankfurt.de)
  • A pathway for stilbene biosynthesis was constructed in Escherichia coli with 4-coumaroyl CoA ligase 1 4CL1) from Arabidopsis thaliana and stilbene synthase (STS) cloned from Arachis hypogaea . (biomedcentral.com)
  • A type III polyketide synthase then sequentially adds three acetate extender units, derived from malonyl-CoA, to a single activated 4-coumaroyl-CoA starter unit. (biomedcentral.com)
  • Depending on the polyketide synthase activity, chalcone synthase (CHS, EC 2.3.1.74) or stilbene synthase (STS, EC 2.3.1.95), subsequent folding and cyclization of the generated tetraketide intermediate results either in the production of a chalcone or stilbene ring structure. (biomedcentral.com)
  • Their carbon framework arises from the polyketide pathway via a polyketide synthase (PKS) that uses an unusual starter unit. (nih.gov)
  • Probing the flexibility of an iterative modular polyketide synthase with non-native substrates in vitro. (lbl.gov)
  • 2014. "In vitro analysis of carboxyacyl substrate tolerance in the loading and first extension modules of Borrelidin polyketide synthase. (lbl.gov)
  • 2014. "Enzyme analysis of the polyketide synthase leads to the discovery of a novel analog of the antibiotic a-lipomycin. (lbl.gov)
  • Finally, combined quantum mechanical/molecular mechanical (QM/MM) modelling of the IdmH reaction shows that the active site of the enzyme provides an appropriate environment to promote indane-ring formation, supporting the assignment of IdmH as the key Diels-Alderase catalysing the final step in the biosynthesis of indanomycin through a similar mechanism to other recently characterized Diels-Alderases involved in polyketide-tailoring reactions. (iucr.org)
  • Built YchM deletion exhibited artificial lethality with multiple fatty acidity biosynthesis genes, as well as the YchM polypeptide bodily interacted numerous proteins from the fatty acidity biosynthetic pathway. (exposed-skin-care.net)
  • Functional characterization of the genes within the ttn gene cluster from Streptomyces griseochromogenes established the biosynthesis of the TTN polyketide backbone, its dialkylmaleic anhydride moiety, the coupling of the two moieties to form the nascent intermediate TTN F-1, and the tailoring steps converting TTN F-1 to TTN. (nycu.edu.tw)
  • TtnD represents the first example of a prFMN-dependent decarboxylase involved in polyketide biosynthesis, expanding the substrate scope of the UbiD family of decarboxylases beyond simple aromatic and cinnamic acids. (nycu.edu.tw)
  • The biosynthesis can be divided into enzymes responsible for the biosynthesis of the core structure (XcnAFHIJKL), including the hydroxymalonyl-ACP (XcnBCDE), in proteins involved in an interesting drug activation mechanism (XcnAG) and for a resistance conferring inactivation pathway (XcnMN). (uni-frankfurt.de)
  • A particular strength of this strategy is that it is always successful: it generates knowledge about the evolution of bioactive-molecule biosynthesis in fungi, it either yields novel molecules or links the studied pathway to already known molecules, and it reveals the chemical diversity within a given pathway, all at once. (knaw.nl)
  • 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)
  • A LAL regulator RimR2 was identified as a positive specific-pathway regulator of rimocidin biosynthesis in M527. (biomedcentral.com)
  • Fungal polyketide biosynthesis - a personal perspective. (shengsci.com)
  • This Viewpoint article provides a personal viewpoint of research in the area of fungal polyketide biosynthesis. (shengsci.com)
  • 2015. "Divergent mechanistic routes for the formation of gem-dimethyl groups in the biosynthesis of complex polyketides. (lbl.gov)
  • Ergothioneine production by Corynebacterium glutamicum harboring heterologous biosynthesis pathways. (hokudai.ac.jp)
  • Dr. Williams is a decorated chemist and is well-known for his innovative work in polyketide biosynthesis, the development of enzymatic tools for protein engineering, and the development of novel biosensors to guide metabolic engineering and high-throughput synthetic biology. (biospace.com)
  • The biosynthetic pathways are implemented in Aspergillus nidulans (filamentous fungus), S. cerevisiae (yeast) or E. coli (bacterium). (dtu.dk)
  • The heterologous expression of the homologue from Aspergillus parvulus linked this pathway to naphthalenone compounds, which were detected in cultures when the pathway was expressed. (knaw.nl)
  • Both pathways were reconstituted step by step in Aspergillus oryzae and the key biosynthetic transformations were adressed through a combination of in vivo and in vitro studies. (uni-hannover.de)
  • including perturbation of genes in biosynthetic gene clusters and regulation for triacylglycerols pool towards armeniaspirol upregulation. (authorea.com)
  • Our unbiased and rational strategy generated evolutionary knowledge that ultimately linked biosynthetic genes to naphthalenone polyketides. (knaw.nl)
  • Phenylpropionic acids, such as 4-coumaric acid and caffeic acid, can be efficiently converted to stilbene compounds by recombinant E. coli cells expressing plant biosynthetic genes. (biomedcentral.com)
  • 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)
  • 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)
  • 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 biosynthetic gene clusters of these linaridins lack obvious candidate genes for the dehydratase and epimerase required to introduce dehydrobutyrine and D-amino acid residues, respectively. (hokudai.ac.jp)
  • However, we previously demonstrated that the grisemycin (grm) cluster contained cryptic dehydratase and epimerase genes by heterologous expression of this biosynthetic gene cluster in Streptomyces lividans and proposed that two genes (grmH and grmL) with unknown functions catalyze dehydration and epimerization reactions. (hokudai.ac.jp)
  • to a membrane-scaffolded organic of fatty acidity biosynthetic enzymes (Babu et al. (exposed-skin-care.net)
  • This includes the mapping of biosynthetic pathways, characterization of involved enzymes, as well as the genetic basis and the evolutionary forces that shape these systems. (dtu.dk)
  • The remarkable diversity of natural products (NPs) results from a similarly diverse pool of biosynthetic enzymes [ 2 ]. (biomedcentral.com)
  • Our work in biochemistry and microbiology focuses on understanding unknown metabolic pathways, enzymes or microbial processes that will be central to be able to engineer new metabolic functions inside cells. (lbl.gov)
  • If we want to produce these natural products using a microbial host, it is essential that we know the natural biosynthetic enzymes and be able to reconstitute those steps in the microbial host. (lbl.gov)
  • When we are faced with unknown pathway enzymes, the Keasling Lab uses a variety of genomics tools and enzyme assays to discover the missing biosynthetic steps. (lbl.gov)
  • With the aim of producing important chemicals in microorganisms, we focus our efforts at investigating novel biochemical pathways and engineering microorganisms to host these pathways. (lbl.gov)
  • The rich chemical and structural diversity of natural products make them attractive sources for biochemical pathways that can lead to novel chemicals. (lbl.gov)
  • Targeted-untargeted approaches combine known metabolites with the untargeted datasets as a hypothesis-generating tool to discover metabolite relationships, clusters, families and biochemical pathways 15 , 18 . (vistagreencg.com)
  • In fungal secondary metabolite systems, we are especially interested in the role of horizontal gene transfer events, the organization of biosynthetic pathways, self-resistance mechanisms and how gene clusters are formed, expand and erode. (dtu.dk)
  • Homologs of CylC are also found in other characterized cyanobacterial secondary metabolite biosynthetic gene clusters. (biomedcentral.com)
  • Only 3 of the clusters produce CBDA in significant quantities while the other 2 clusters redirect metabolic resources toward the THCA production pathways. (vistagreencg.com)
  • The lecture deals with basic biosynthetic principles and metabolic intersections of primary and secondary metabolism. (uni-leipzig.de)
  • The applied research aims at developing general strategies/tools for implementing and designing synthetic pathways for the production of natural and new-to-nature compounds. (dtu.dk)
  • During this work, xenocoumacin 1 (XCN 1) and 2 (XCN 2), the major antimicrobial compounds produced by Xenorhabdus nematophila and their corresponding biosynthetic gene cluster were identified and studied in detail. (uni-frankfurt.de)
  • An omics strategy has been applied to accelerate the progress of pathway dissection for many important bioactive compounds, for example, ginsenoside, vinblastine, artemisinin and cannabinoids. (biomedcentral.com)
  • Heterologous expression and precursor incubation experiments led to the elucidation of the biosynthetic steps of streptoazine C. In vivo biotransformation experiments proved the high flexibility of the prenyltransferase SasB toward tryptophan-containing cyclodipeptides and their dehydroderivatives for regular C-3-prenylation. (uni-marburg.de)
  • However, the emergence of several CRISPR-Cas9-based genome editing systems adapted for several genera of filamentous fungi have now opened the doors for future efforts in discovery of novel natural products and elucidation and engineering of their biosynthetic pathways in fungi where no genetic tools are in place. (unl.edu)
  • Modifications on the core structure by an aryl acid reductase (UttJ), a putative nonheme FeII/2-oxoglutarate dependent oxygenase (UttH), a cytochrome P450 enzyme (UttC) and a O-methyltransferase (UttF) led to the final product ustethylin A. This study is the first report on the biosynthetic pathway of a phenethyl-containing natural product. (uni-marburg.de)
  • You will learn how to identify building blocks of natural products, build biosynthetic proposals, and suggest enzyme mechanisms. (uni-leipzig.de)
  • in filamentous fungi, the his-asp phosphorelay signaling system and hog pathway are involved in the action of the fungicides, fludioxonil, and iprodione, as well as osmotic and oxidative stress responses. (liverpool.ac.uk)
  • Their biosynthetic pathways are not fully elucidated but thanks to recent genomic approaches combined to the increasing genome sequencing of fungi some of them have been recently unveiled. (hal.science)
  • abstract = "Tautomycetin (TTN) is a polyketide natural product featuring a terminal alkene. (nycu.edu.tw)
  • An example of these bioactive scaffolds are armeniaspirols, which are potent polyketide antibiotics against gram-positive pathogens and multi-resistance gram-negative Helicobacter pylori . (authorea.com)
  • Covering: up to 2017This review covers the biosynthetic and evolutionary aspects of lincosamide antibiotics, antitumour pyrrolobenzodiazepines (PBDs) and the quorum-sensing molecule hormaomycin. (shengsci.com)
  • The clb pathway is found in gut commensal Escherichia coli, and clb metabolites are thought to initiate colorectal cancer via DNA crosslinking. (omicsdi.org)
  • Certain commensal Escherichia coli contain the clb biosynthetic gene cluster that codes for small molecule prodrugs known as precolibactins. (omicsdi.org)
  • This cleavage pathway forms other known clb metabolites or biosynthetic intermediates and explains the difficulties in isolating fully mature biosynthetic products. (omicsdi.org)
  • Specifically, we exploit CRISPR-Cas9-based genome editing to identify a new gene in T. atroroseus responsible for production of polyketide-nonribosomal peptide hybrid products, hence, linking fungal secondary metabolites to their genetic origin in a species where no genetic engineering has previously been performed. (unl.edu)
  • 2010). ACP and fatty acyl-coA transferases may also be needed at multiple levels of microbial polyketide synthesis. (exposed-skin-care.net)
  • It is our vision to create a series of programmable microbial platforms that allows for the synthesis of any biological relevant carbon skeleton, thereby bypassing the time-consuming task of identifying natural pathways. (dtu.dk)
  • This knowledge allows prioritizing the choice of the pathway to functionally characterize in a second stage using synthetic-biology tools like heterologous expression. (knaw.nl)
  • Five different prexenocoumacins are formed by the xenocoumacin biosynthetic machinery as inactive prodrugs inside the cytoplasm. (uni-frankfurt.de)
  • a highly rearranged polyketide antibiotic derived from the angucycline backbone that is synthesized via several yet unexplained enzymatic reactions. (unibas.ch)
  • We also know that Norbaeocystin and Baeocystin are intermediary steps in the organic synthesis of psilocybin and thus all species that use this pathway contain trace amounts. (shroomery.org)
  • Instead, we propose that these are off-pathway fermentation products produced by a facile double cyclodehydration route that manifests in the absence of viable ClbP. (omicsdi.org)
  • The biosynthetic pathways for some of the most important natural products from plants are not known. (lbl.gov)
  • Cannabinoids are synthesized in acidic forms through the condensation of geranyl diphosphate (GPP) and most commonly olivetolic acid, products of the methylerythritol phosphate (MEP) and polyketide pathways 11 , 12 . (vistagreencg.com)
  • The biosynthetic platform developed by Dr. Gavin Williams provides a potential simple and efficient method for rapidly producing natural products, such as psilocybin, using an engineered enzymatic pathway in E. coli . (biospace.com)
  • Here, the products of the ADH pathway will be used to generate key building blocks for psilocybin and its derivatives. (biospace.com)
  • The determination of the evolutionary relationships of aromatic polyketide pathways resulted in the identification of an uncharacterized biosynthetic pathway that is conserved in distant fungal lineages. (knaw.nl)
  • Our approach is to first determine the evolutionary relationships of fungal biosynthetic pathways in order to identify those that are already characterized and those that show a different evolutionary origin. (knaw.nl)
  • Dr. Williams and his team recently developed an artificial enzymatic platform called the 'Alcohol Dependent Hemiterpene' pathway for construction of alkyl pyrophosphates. (biospace.com)
  • Principles of natural product discovery and biosynthetic engineering will be covered. (uni-leipzig.de)
  • The Biosynthetic Pathway Engineering research group is committed to further our understanding of biosynthetic pathways, and to utilize this knowledge to implement natural biosynthetic pathways and for the design of artificial (synthetic) pathways for the production of small molecules. (dtu.dk)
  • The goal is to engineer E. coli to be a factory for psilocybin production, using a completely artificial biosynthetic logic. (biospace.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)
  • The strategy is very powerful to avoid studying the same pathway again and can be used with any fungal genome. (knaw.nl)
  • Together, these data indicate the domestication of the cannabis germplasm has resulted in a loss of the CBDA pathway in some strains and reallocation of resources between CBDA and THCA pathways in others. (vistagreencg.com)
  • Here we report confirmation of the structural assignment of the complex clb product precolibactin 886 via a biomimetic synthetic pathway. (omicsdi.org)
  • The colibactin peptidase ClbP deacylates synthetic precolibactin 886 to form a non-genotoxic pyridone, which suggests precolibactin 886 lies off the path of the major biosynthetic route. (omicsdi.org)
  • With either overexpression of extender unit pathway or late-stage N -methylation, or the deletion of a competing polyketide cluster, we can achieve 7-49-fold upregulation of armeniaspirols production. (authorea.com)
  • both TtnD and TtnC are encoded within the ttn biosynthetic gene cluster. (nycu.edu.tw)
  • In this study, using domain structure and amino acid alignment and phylogenetic tree construction, rimR 2, which located in the rimocidin biosynthetic gene cluster, was first found and identified as a larger ATP-binding regulators of the LuxR family (LAL) subfamily regulator. (biomedcentral.com)
  • Tylosin production is evidently controlled by pathway-specific and pleiotropic regulators with the likely involvement of y-butyrolactone signalling factors. (nih.gov)
  • We expect that the library will be an important resource towards a systemic understanding of polyketide production in A. nidulans. (dna-metabolism.com)