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polyketide synthase

Omar Santín, Gabriel Moncalián
Omega-3 polyunsaturated fatty acids (PUFA) are produced in some unicellular organisms, such as marine gammaproteobacteria, myxobacteria and thraustochytrids, by large enzyme complexes called PUFA synthases. These enzymatic complexes resemble bacterial antibiotic-producing proteins known as polyketide synthases (PKS). One of the PUFA synthase subunits is a conserved large protein (PfaA in marine proteobacteria) that contains three to nine tandem Acyl Carrier Protein domains as well as condensation and modification domains...
June 19, 2018: Journal of Biological Chemistry
Michael W Mullowney, Ryan A McClure, Matthew T Robey, Neil L Kelleher, Regan J Thomson
Covering: up to 2018Thioester reductase domains catalyze two- and four-electron reductions to release natural products following assembly on nonribosomal peptide synthetases, polyketide synthases, and their hybrid biosynthetic complexes. This reductive off-loading of a natural product yields an aldehyde or alcohol, can initiate the formation of a macrocyclic imine, and contributes to important intermediates in a variety of biosyntheses, including those for polyketide alkaloids and pyrrolobenzodiazepines. Compounds that arise from reductase-terminated biosynthetic gene clusters are often reactive and exhibit biological activity...
June 19, 2018: Natural Product Reports
A Bouam, N Armstrong, A Levasseur, M Drancourt
Three slowly growing mycobacteria named strain AB308, strain AB215 and strain AB57 were isolated from the tomato plant roots. The 16S rRNA and rpoB gene sequence analyses suggested that each strain was representative of one hitherto unidentified slowly-growing Mycobacterium species of the Mycobacterium simiae complex. Genome sequencing indicated that each strain contained one chromosome of 6.015-6.029 Mbp. A total of 1,197, 1,239 and 1,175 proteins were found to be associated with virulence and 107, 76 and 82 proteins were associated with toxin/antitoxin systems for strains AB308, AB215 and AB57, respectively...
June 18, 2018: Scientific Reports
Samuel C Curran, Andrew Hagen, Sean Poust, Leanne Jade G Chan, Brett M Garabedian, Tristan de Rond, Marian-Joy Baluyot, Jonathan T Vu, Andrew K Lau, Satoshi Yuzawa, Christopher J Petzold, Leonard Katz, Jay D Keasling
In the search for molecular machinery for custom biosynthesis of valuable compounds, the modular Type I polyketide synthases (PKSs) offer great potential. In this study we investigate the flexibility of BorM5, the iterative fifth module of the borrelidin synthase, with a panel of non-native priming substrates in vitro. BorM5 differentially extends various aliphatic and substituted substrates. Depending on substrate size and substitution BorM5 can exceed the three iterations it natively performs. To probe the effect of methyl branching on chain length regulation we engineered a BorM5 variant capable of incorporating methylmalonyl- and malonyl-CoA into its intermediates...
June 18, 2018: ACS Chemical Biology
Fabian Panter, Daniel Krug, Sascha Baumann, Rolf Müller
There is astounding discrepancy between the genome-inscribed production capacity and the set of known secondary metabolite classes from many microorganisms as detected under laboratory cultivation conditions. Genome-mining techniques are meant to fill this gap, but in order to favor discovery of structurally novel as well as bioactive compounds it is crucial to amend genomics-based strategies with selective filtering principles. In this study, we followed a self-resistance guided approach aiming at the discovery of inhibitors of topoisomerase, known as valid target in both cancer and antibiotic therapy...
June 7, 2018: Chemical Science
Marco N Allemann, Eric E Allen
The long-chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFAs) EPA (20:5n-3) and DHA (22:6n-3) are widely recognized as beneficial to human health and development. Select lineages of cosmopolitan marine prokaryotic and eukaryotic microorganisms synthesize these compounds via a unique fatty acid synthase/polyketide synthase mechanism that is distinct from the canonical desaturase/elongase-mediated pathway employed by the majority of eukaryotic single-cell microorganisms and metazoans. This "Pfa synthase" mechanism is highly efficient and has been co-opted for the large-scale industrial production of n-3 LC-PUFAs for commercial applications...
2018: Methods in Enzymology
Jeong Ho Kim, Mamoru Komatsu, Kazuo Shin-Ya, Satoshi Omura, Haruo Ikeda
Phosphopantetheinyl transferases (PPTases) are a superfamily of essential enzymes required for the synthetic processes of many compounds including fatty acid, polyketide, and nonribosomal peptide metabolites. These enzymes activate carrier proteins in specific biosynthetic pathways via the transfer of a phosphopantetheinyl moiety to a serine residue in the conserved motif of carrier proteins. Since many Actinomycetales microorganisms produce a number of polyketide and nonribosomal peptide metabolites, the distribution of PPTase genes was investigated in these microorganisms...
June 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
Alexander Crits-Christoph, Spencer Diamond, Cristina N Butterfield, Brian C Thomas, Jillian F Banfield
In soil ecosystems, microorganisms produce diverse secondary metabolites such as antibiotics, antifungals and siderophores that mediate communication, competition and interactions with other organisms and the environment1,2 . Most known antibiotics are derived from a few culturable microbial taxa 3 , and the biosynthetic potential of the vast majority of bacteria in soil has rarely been investigated 4 . Here we reconstruct hundreds of near-complete genomes from grassland soil metagenomes and identify microorganisms from previously understudied phyla that encode diverse polyketide and nonribosomal peptide biosynthetic gene clusters that are divergent from well-studied clusters...
June 13, 2018: Nature
Roy A Meoded, Reiko Ueoka, Eric J N Helfrich, Katja Jensen, Nancy Magnus, Birgit Piechulla, Jörn Piel
Enzymatic core components from trans-acyltransferase polyketide synthases (trans-AT PKSs) catalyze exceptionally diverse biosynthetic transformations to generate structurally complex bioactive compounds. Here we focus on a group of oxygenases identified in various trans-AT PKS pathways, including those for pederin, oocydins, and toblerols. Using the oocydin pathway homolog (OocK) from Serratia plymuthica 4Rx13 and N-acetylcysteamine (SNAC) thioesters as test surrogates for acyl carrier protein-tethered intermediates, we show that the enzyme inserts oxygen into β-ketoacyl moieties to yield malonyl ester SNAC products...
June 13, 2018: Angewandte Chemie
Srividhya Sundaram, Hak Joong Kim, Ruth Bauer, Tawatchai Thongkongkaew, Daniel Heine, Christian Hertweck
Ketosynthase (KS) domains of modular type I polyketide synthases (PKSs) typically catalyze Claisen condensation of acyl and malonyl units to form linear chains. In stark contrast, the KS domain of the rhizoxin PKS branching module installs a β-branch by a Michael-type vinylogous addition, which sets the basis for a pharmacophoric δ-lactone moiety. The precise role of the KS domain was evaluated by site-directed mutagenesis, chemical probes, and biotransformations. Biochemical and kinetic analyses helped dissecting branching and lactonization reactions, and unequivocally assigned the entire reaction sequence to the KS...
June 13, 2018: Angewandte Chemie
Naruo Nikoh, Tsutomu Tsuchida, Taro Maeda, Katsushi Yamaguchi, Shuji Shigenobu, Ryuichi Koga, Takema Fukatsu
Members of the genus Rickettsiella are bacterial pathogens of insects and other arthropods. Recently, a novel facultative endosymbiont, " Candidatus Rickettsiella viridis," was described in the pea aphid Acyrthosiphon pisum , whose infection causes a striking host phenotype: red and green genetic color morphs exist in aphid populations, and upon infection with the symbiont, red aphids become green due to increased production of green polycyclic quinone pigments. Here we determined the complete genome sequence of the symbiont...
June 12, 2018: MBio
Deokhee Jo, Sunkyu Han
Since the first isolation of pseurotin A in 1976, over twenty five spirocyclic PKS-NRPS-based (polyketide synthase-nonribosomal peptide synthetase-based) fungal natural products have been discovered to date. The common 1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione core of this family of natural products has served as a platform for the development of novel chemistry and resulted in the development of numerous new reactivities and synthetic strategies. Herein, we delineate all reported syntheses of spirocyclic PKS-NRPS-based fungal metabolites including our own recent contributions on this subject...
June 6, 2018: Chemical Communications: Chem Comm
Akimasa Miyanaga, Risako Ouchi, Fumihiro Ishikawa, Ena Goto, Genzoh Tanabe, Fumitaka Kudo, Tadashi Eguchi
Acyltransferases (ATs) are responsible for the selection and incorporation of acyl building blocks in the biosynthesis of various polyketide natural products. The trans-AT modular polyketide synthases have a discrete trans-acting AT for the loading of an acyl unit onto the acyl carrier protein (ACP) located within each module. Despite the importance of protein-protein interactions between ATs and ACPs in trans-AT assembly lines, the dynamic actions of ACPs and trans-acting ATs remain largely uncharacterized because of the inherently transient nature of ACP-enzyme interactions...
June 5, 2018: Journal of the American Chemical Society
Osama A A Mohamad, Li Li, Jin-Biao Ma, Shaimaa Hatab, Lin Xu, Jian-Wei Guo, Bakhtiyor A Rasulov, Yong-Hong Liu, Brian P Hedlund, Wen-Jun Li
Endophytic bacteria associated with medicinal plants possess unique strategies that enhance growth and suvival of host plants, many of which are mediated by distinctive secondary metabolites. These bacteria and their secondary metabolites are important subjects for both basic and applied research aimed at sustainable agriculture. In the present study, 114 endophytic strains isolated from the wild ethnomedicinal plant Glycyrrhiza uralensis (licorice) were screened for their in vitro antimicrobial activities against common fungal pathogens of tomato ( Fusarium oxysporum f...
2018: Frontiers in Microbiology
Dhivya Ramakrishnan, Manish K Tiwari, Gomathi Manoharan, Thiagarajan Sairam, Rajesh Thangamani, Jung-Kul Lee, Jeya Marimuthu
Two putative type III polyketide synthase genes (PKS) were identified from Sordariomycetes fungi. These two type III PKS genes from Sordaria macrospora (SmPKS) and Chaetomium thermophilum (CtPKS), shared 59.8% sequence identity. Both, full-length and truncated versions of type III PKSs were successfully cloned and overexpressed in a bacterial host, Escherichia Coli BL21 (DE3) using a N-terminus hexa-histidine tag. The full-length and the truncated construct of PKSs showed similar activity profiles, suggesting that additional amino acid residues at the C-terminal of both SmPKS and CtPKS may not be involved in catalytic functions...
August 2018: Enzyme and Microbial Technology
Monika Schmoll
Trichoderma reesei represents one of the most prolific producers of homologous and heterologous proteins. Discovery of the photoreceptor ENV1 as a regulator of cellulase gene expression initiated analysis of light response pathways and their physiological relevance for T. reesei. The function of ENV1 in regulation of plant cell wall degrading enzymes is conserved in Neurospora crassa. ENV1 emerged as a central checkpoint for integration of nutrient sensing, light response and development. This photoreceptor exerts its function by influencing transcript abundance and feedback cycles of the alpha subunits of the heterotrimeric G-protein pathway and impacts regulation of the beta and gamma subunits via mutual regulation with the phosducin PhLP1...
June 2018: Fungal Biology
Ge Liao, Wen-Hua Dong, Jin-Ling Yang, Wei Li, Jun Wang, Wen-Li Mei, Hao-Fu Dai
Agarwood is highly valued for its uses as incense, perfume, and medicine. However, systematic analyses of dynamic changes of secondary metabolites during the process of agarwood formation have not yet been reported. In this study, agarwood was produced by transfusing the agarwood inducer into the trunk of Aquilaria sinensis , and changing patterns of chemical constituents, especially 2-(2-phenylethyl)chromones (PECs), in wood samples collected from the 1st to 12th month, were analyzed by GC-EI-MS and UPLC-ESI-MS/MS methods...
May 25, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Huiming Ge, Xuan Zhang, Tingting Wang, Qin Lan Xu, Ying Xiong, Li Zhang, Hao Han, Kuang Xu, Wen Jie Guo, Qiang Xu, Ren Xiang Tan
Two homologous meroterpenoid gene clusters consisting of contiguous genes encoding polyketide synthase (PKS), prenyltransferase (PT), terpenoid cyclase (TC) and other tailoring enzymes were identified from two phylogenetically distinct fungi through in silico analysis. Media optimization guided by reverse transcription-PCR (RT-PCR) enabled two strains to produce eight new and two known meroterpenoids (1-10). Using in vivo gene inactivation, heterologous expression and in vitro biochemical analyses, we revealed a new polyketide-terpenoid assembly line that utilizes a pair of PKSs to synthesize 2,4-dihydroxy-6-alkylbenzoic acid, followed by oxidative decarboxylation, farnesyl transfer, as well as terpene cyclization to construct the meroterpenoid scaffold...
May 24, 2018: Angewandte Chemie
Chettida Srisuksam, Juntira Punya, Songsak Wattanachaisaereekul, Wachiraporn Toopaang, Supapon Cheevadhanarak, Morakot Tanticharoen, Alongkorn Amnuaykanjanasin
pks14, a reducing clade IIb polyketide synthase gene, is preserved throughout the evolution of entomopathogenic fungi. We examined the functions of pks14 in Beauveria bassiana using targeted gene disruption. pks14 disruption was verified by Southern blot and PCR analyses. The radial growth, cell dry weight and conidial germination of Δpks14 were comparable to that of the wild type. Our sequence and gene expression analyses of the pks14 biosynthetic cluster demonstrated: (i) cotranscription and constitutive expression of nearly all genes of the aforementioned cluster including C2H2 zinc finger transcription regulator gene, but not pks14 and cytochrome P450 gene; (ii) expression of pks14 gene in insect-containing culture condition only; whereby (iii) a KAR9-like gene in direct proximity with pks14 is the only gene showing co-regulation...
May 22, 2018: FEMS Microbiology Letters
Ghofran Othoum, Salim Bougouffa, Rozaimi Razali, Ameerah Bokhari, Soha Alamoudi, André Antunes, Xin Gao, Robert Hoehndorf, Stefan T Arold, Takashi Gojobori, Heribert Hirt, Ivan Mijakovic, Vladimir B Bajic, Feras F Lafi, Magbubah Essack
BACKGROUND: The increasing spectrum of multidrug-resistant bacteria is a major global public health concern, necessitating discovery of novel antimicrobial agents. Here, members of the genus Bacillus are investigated as a potentially attractive source of novel antibiotics due to their broad spectrum of antimicrobial activities. We specifically focus on a computational analysis of the distinctive biosynthetic potential of Bacillus paralicheniformis strains isolated from the Red Sea, an ecosystem exposed to adverse, highly saline and hot conditions...
May 22, 2018: BMC Genomics
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