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polyketide synthase

Pooja Gopal, Michelle Yee, Jickky Sarathy, Jian Liang Low, Jansy P Sarathy, Firat Kaya, Véronique Dartois, Martin Gengenbacher, Thomas Dick
Pyrazinamide (PZA) is a critical component of first- and second-line treatments of tuberculosis (TB), yet its mechanism of action largely remains an enigma. We carried out a genetic screen to isolate Mycobacterium bovis BCG mutants resistant to pyrazinoic acid (POA), the bioactive derivative of PZA, followed by whole genome sequencing of 26 POA resistant strains. Rather than finding mutations in the proposed candidate targets fatty acid synthase I and ribosomal protein S1, we found resistance conferring mutations in two pathways: missense mutations in aspartate decarboxylase panD, involved in the synthesis of the essential acyl carrier coenzyme A (CoA), and frameshift mutations in the vitro nonessential polyketide synthase genes mas and ppsA-E, involved in the synthesis of the virulence factor phthiocerol dimycocerosate (PDIM)...
September 9, 2016: ACS Infectious Diseases
Simón Menendez-Bravo, Julia Roulet, Martín Sabatini, Santiago Comba, Robert Dunn, Hugo Gramajo, Ana Arabolaza
BACKGROUND: Microbial synthesis of oleochemicals derived from native fatty acid (FA) metabolism has presented significant advances in recent years. Even so, native FA biosynthetic pathways often provide a narrow variety of usually linear hydrocarbons, thus yielding end products with limited structural diversity. To overcome this limitation, we took advantage of a polyketide synthase-based system from Mycobacterium tuberculosis and developed an Escherichia coli platform with the capacity to synthesize multimethyl-branched long-chain esters (MBE) with novel chemical structures...
2016: Biotechnology for Biofuels
Yemin Wang, Zhengsheng Tao, Hualiang Zheng, Fei Zhang, Qingshan Long, Zixin Deng, Meifeng Tao
Many high-value secondary metabolites are assembled by very large multifunctional polyketide synthases or non-ribosomal peptide synthetases encoded by giant genes, for instance, natamycin production in an industrial strain of Streptomyces gilvosporeus. In this study, a large operon reporter-based selection system has been developed using the selectable marker gene neo to report the expression both of the large polyketide synthase genes and of the entire gene cluster, thereby facilitating the selection of natamycin-overproducing mutants by iterative random mutagenesis breeding...
October 13, 2016: Metabolic Engineering
Hisayuki Komaki, Akira Hosoyama, Natsuko Ichikawa, Yasuhiro Igarashi
Here, we report the draft genome sequence of Bacillus subtilis TP-B0611, which produces the isocoumarin-type compounds bacilosarcin and amicoumacin. The genome encodes three nonribosomal peptide synthetase (NRPS) gene clusters and one hybrid polyketide synthase (PKS)/NRPS gene cluster. The hybrid PKS/NRPS gene cluster was identified to be responsible for the biosynthesis of bacilosarcins and amicoumacins.
October 13, 2016: Genome Announcements
Hisayuki Komaki, Akira Hosoyama, Natsuko Ichikawa, Watanalai Panbangred, Yasuhiro Igarashi
We report here the draft genome sequence of Streptomyces sp. SPMA113 isolated from soil in Thailand. This strain produces a new modified peptide, prajinamide, which has adipocyte differentiation activity. The genome harbors at least 30 gene clusters for synthases of polyketide and nonribosomal peptide, suggesting its potential to produce diverse secondary metabolites.
October 13, 2016: Genome Announcements
Yu Nakashima, Yoko Egami, Miki Kimura, Toshiyuki Wakimoto, Ikuro Abe
Sponge metagenomes are a useful platform to mine cryptic biosynthetic gene clusters responsible for production of natural products involved in the sponge-microbe association. Since numerous sponge-derived bioactive metabolites are biosynthesized by the symbiotic bacteria, this strategy may concurrently reveal sponge-symbiont produced compounds. Accordingly, a metagenomic analysis of the Japanese marine sponge Discodermia calyx has resulted in the identification of a hybrid type I polyketide synthase-nonribosomal peptide synthetase gene (kas)...
2016: PloS One
Futoshi Taura, Miu Iijima, Eriko Yamanaka, Hironobu Takahashi, Hiromichi Kenmoku, Haruna Saeki, Satoshi Morimoto, Yoshinori Asakawa, Fumiya Kurosaki, Hiroyuki Morita
Rhododendron dauricum L. produces daurichromenic acid, the anti-HIV meroterpenoid consisting of sesquiterpene and orsellinic acid (OSA) moieties. To characterize the enzyme responsible for OSA biosynthesis, a cDNA encoding a novel polyketide synthase (PKS), orcinol synthase (ORS), was cloned from young leaves of R. dauricum. The primary structure of ORS shared relatively low identities to those of PKSs from other plants, and the active site of ORS had a unique amino acid composition. The bacterially expressed, recombinant ORS accepted acetyl-CoA as the preferable starter substrate, and produced orcinol as the major reaction product, along with four minor products including OSA...
2016: Frontiers in Plant Science
Zifei Xu, Yonghong Chen, Tianyang Song, Zhijun Zeng, Ni Yan, Keqin Zhang, Xuemei Niu
Arthrobotrys oligospora is the first recognized nematode-trapping fungus and by far the most abundant in the environment. Our recent study revealed the polyketide synthase (PKS) gene AOL_s00215g283 in A. oligospora involved in the production of many secondary metabolites and the trap formation of the fungus. Here we report that the disruption of two genes in the upstream flanking region of the gene AOL_s00215g283, AOL_s00215g281 and AOL_s00215g282, which putatively encoded one amidohydrolase and one cytochrome P450 monooxygenase, respectively, both resulted in significant nematicidal activity of the cultural broths of the mutants and loss of morphological regulatory arthrosporols...
October 11, 2016: Journal of Agricultural and Food Chemistry
Meredith A Skiba, Andrew P Sikkema, William D Fiers, William H Gerwick, David H Sherman, Courtney C Aldrich, Janet L Smith
Polyketide metabolites produced by modular type I polyketide synthases (PKS) acquire their chemical diversity through the variety of catalytic domains within modules of the pathway. Methyltransferases are among the least characterized of the catalytic domains common to PKS systems. We determined the domain boundaries and characterized the activity of a PKS C-methyltransferase (C-MT) from the curacin A biosynthetic pathway. The C-MT catalyzes S-adenosylmethionine-dependent methyl transfer to the α-position of β-ketoacyl substrates linked to acyl carrier protein (ACP) or a small-molecule analog, but does not act on β-hydroxyacyl substrates or malonyl-ACP...
October 10, 2016: ACS Chemical Biology
Marta Maciejewska, Delphine Adam, Loïc Martinet, Aymeric Naômé, Magdalena Całusińska, Philippe Delfosse, Monique Carnol, Hazel A Barton, Marie-Pierre Hayette, Nicolas Smargiasso, Edwin De Pauw, Marc Hanikenne, Denis Baurain, Sébastien Rigali
Moonmilk speleothems of limestone caves host a rich microbiome, among which Actinobacteria represent one of the most abundant phyla. Ancient medical texts reported that moonmilk had therapeutical properties, thereby suggesting that its filamentous endemic actinobacterial population might be a source of natural products useful in human treatment. In this work, a screening approach was undertaken in order to isolate cultivable Actinobacteria from moonmilk of the Grotte des Collemboles in Belgium, to evaluate their taxonomic profile, and to assess their potential in biosynthesis of antimicrobials...
2016: Frontiers in Microbiology
Yu-Rong Cheng, Zhi-Jie Sun, Gu-Zhen Cui, Xiaojin Song, Qiu Cui
Developing a strain with high docosahexaenoic acid (DHA) yield and stable fermenting-performance is an imperative way to improve DHA production using Aurantiochytrium sp., a microorganism with two fatty acid synthesis pathways: polyketide synthase (PKS) pathway and Type I fatty acid synthase (FAS) pathway. This study investigated the growth and metabolism response of Aurantiochytrium sp. CGMCC 6208 to two inhibitors of enoyl-ACP reductase of Type II FAS pathway (isoniazid and triclosan), and proposed a method of screening high DHA yield Aurantiochytrium sp...
November 2016: Enzyme and Microbial Technology
Mahsa Mir Mohseni, Thomas Höver, Lena Barra, Marcel Kaiser, Pieter C Dorrestein, Jeroen S Dickschat, Till F Schäberle
The biosynthetic gene cluster for the antiplasmodial natural product siphonazole was identified by using a combination of genome mining, imaging, and expression studies in the natural producer Herpetosiphon sp. B060. The siphonazole backbone is assembled from an unusual starter unit from the shikimate pathway that is extended by the action of polyketide synthases and non-ribosomal peptide synthetases with unusual domain structures, including several split modules and a large number of duplicated domains and domains predicted to be inactive...
October 17, 2016: Angewandte Chemie
Yun-Feng Peng, Wen-Chao Chen, Kang Xiao, Lin Xu, Lian Wang, Xia Wan
The gene encoding phosphopantetheinyl transferase (PPTase), pfaE, a component of the polyketide synthase (PKS) pathway, is crucial for the production of docosahexaenoic acid (DHA, 22:6ω3), along with the other pfa cluster members pfaA, pfaB, pfaC and pfaD. DHA was produced in Escherichia coli by co-expressing pfaABCD from DHA-producing Colwellia psychrerythraea 34H with one of four pfaE genes from bacteria producing arachidonic acid (ARA, 20:4ω6), eicosapentaenoic acid (EPA, 20:5ω3) or DHA, respectively...
2016: PloS One
Perng-Kuang Chang, Leslie L Scharfenstein, Kenneth C Ehrlich, José Diana Di Mavungu
Aspergillus flavus is able to synthesize a variety of polyketide-derived secondary metabolites including the hepatocarcinogen, aflatoxin B1. The fungus reproduces and disseminates predominantly by production of conidia. It also produces hardened mycelial aggregates called sclerotia that are used to cope with unfavourable growth environments. In the present study, we examined the role of A. flavus fluP, the backbone polyketide synthase gene of secondary metabolite gene cluster 41, on fungal development. The A...
October 2016: Fungal Biology
Veerle E T Maervoet, Yves Briers
The evolution of natural modular proteins and domain swapping by protein engineers have shown the disruptive potential of non-homologous recombination to create proteins with novel functions or traits. Bacteriophage endolysins, cellulosomes and polyketide synthases are 3 examples of natural modular proteins with each module having a dedicated function. These modular architectures have been created by extensive duplication, shuffling of domains and insertion/deletion of new domains. Protein engineers mimic these natural processes in vitro to create chimeras with altered properties or novel functions by swapping modules between different parental genes...
September 20, 2016: Bioengineered
Muhd Danish-Daniel, Gan Han Ming, Mohd Ezhar Mohd Noor, Yik Sung Yeong, Gires Usup
Mameliella alba strain UMTAT08 was isolated from clonal culture of paralytic shellfish toxin producing dinoflagellate, Alexandrium tamiyavanichii. Genome of the strain UMTAT08 was sequenced in order to gain insights into the dinoflagellate-bacteria interactions. The draft genome sequence of strain UMTAT08 contains 5.84Mbp with an estimated G + C content of 65%, 5717 open reading frames, 5 rRNAs and 49 tRNAs. It contains genes related to nutrients uptake, quorum sensing and environmental tolerance related genes...
December 2016: Genomics Data
Lulu Xie, Pingli Liu, Zhixin Zhu, Shifan Zhang, Shujiang Zhang, Fei Li, Hui Zhang, Guoliang Li, Yunxiao Wei, Rifei Sun
Polyketide synthases (PKSs) utilize the products of primary metabolism to synthesize a wide array of secondary metabolites in both prokaryotic and eukaryotic organisms. PKSs can be grouped into three distinct classes, types I, II, and III, based on enzyme structure, substrate specificity, and catalytic mechanisms. The type III PKS enzymes function as homodimers, and are the only class of PKS that do not require acyl carrier protein. Plant type III PKS enzymes, also known as chalcone synthase (CHS)-like enzymes, are of particular interest due to their functional diversity...
2016: Frontiers in Plant Science
Young Ji Yoo, Hanseong Kim, Sung Ryeol Park, Yeo Joon Yoon
Rapamycin is an immunosuppressive metabolite produced from several actinomycete species. Besides its immunosuppressive activity, rapamycin and its analogs have additional therapeutic potentials, including antifungal, antitumor, neuroprotective/neuroregenerative, and lifespan extension activities. The core structure of rapamycin is derived from (4R,5R)-4,5-dihydrocyclohex-1-ene-carboxylic acid that is extended by polyketide synthase. The resulting linear polyketide chain is cyclized by incorporating pipecolate and further decorated by post-PKS modification enzymes...
September 9, 2016: Journal of Industrial Microbiology & Biotechnology
Jakob Weber, Vito Valiante, Christina Spuur Nødvig, Derek Joseph Mattern, Rebecca A Slotkowski, Uffe H Mortensen, Axel A Brakhage
Filamentous fungi produce varieties of natural products even in a strain dependent manner. However, the genetic basis of chemical speciation between strains is still widely unknown. One example is trypacidin, a natural product of the opportunistic human pathogen Aspergillus fumigatus, which is not produced amongst different isolates. Combining computational analysis with targeted gene editing, we could link a single nucleotide insertion in the polyketide synthase of the trypacidin biosynthetic pathway and reconstitute its production in a nonproducing strain...
September 9, 2016: ACS Synthetic Biology
Anyarat Thanapipatsiri, Juan Pablo Gomez-Escribano, Lijiang Song, Maureen Bibb, Mahmoud Al-Bassam, Govind Chandra, Arinthip Thamchaipenet, Greg Challis, Mervyn Bibb
Comparative transcriptional profiling of a ΔbldM mutant of Streptomyces venezuelae with its unmodified progenitor revealed that the expression of a cryptic biosynthetic gene cluster containing both Type I and Type III polyketide synthase genes is activated in the mutant. The 29.5 kb gene cluster, which was predicted to encode an unusual biaryl metabolite, venemycin, and potentially halogenated derivatives, contains 17 genes including one, vemR, encoding a transcriptional activator of the large ATP-binding LuxR-like (LAL) family...
September 8, 2016: Chembiochem: a European Journal of Chemical Biology
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