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https://www.readbyqxmd.com/read/28561936/a-fad-linked-oxidoreductase-enables-an-extracellular-deamination-after-saframycin-a-maturation
#1
Gong-Li Tang, Li-Qiang Song, Ying-Ying Zhang, Jin-Yue Pu, Man-Cheng Tang, Chao Peng
Biosynthesis of antibiotics in bacteria is usually believed as an intracellular process, which ends by exporting the matured compounds outside the cells. The biosynthesis of saframycin A (SFM-A), an antitumor antibiotic, requires a cryptic fatty acyl chain to guide the construction of the pentacyclic tetrahydroisoquinoline scaffold; however, the follow-up deacylation and deamination steps remain unknown. Herein we demonstrate that SfmE, a membrane-bound peptidase, hydrolyzes the fatty acyl chain to release the amino group; and SfmCy2, a secreted oxidoreductase with covalent association of FAD, subsequently performs an oxidative deamination extracellularly...
May 31, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28476707/activation-and-comparative-analysis-of-cryptic-xiamycin-gene-cluster-from-marine-derived-streptomyces-sp-fxj-7-388
#2
Yuhong Uhong Lü, Xiaoli Liu, Miao Wang, Yuanyuan Li, Ning Liu, Yuxin Bao, Minghao Liu, Xiaoqian Li, Yinyin Wang, Shenyan Qian, Changwu Yue, Ying Huang
In order to obtain the natural products synthesized by the three putative xiamycin biosynthesis gene clusters which were predicted via antiSMASH during the genome mining of marine Streptomyces sp. FXJ 7.388, Streptomyces sp. FXJ 8.012, and Streptomyces olivaceus FXJ 7.023. Sixteen genes involved in xiamycin assembly, modification, and regulation with higher identity than the newest reported xiamycin biosynthetic gene cluster from marine Streptomyces sp. SCSIO 02999, Streptomyces sp. HKI0576, and Streptomyces sp...
September 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28404998/a-single-biochemical-activity-underlies-the-pleiotropy-of-the-aging-related-protein-clk-1
#3
Ju-Ling Liu, Callista Yee, Ying Wang, Siegfried Hekimi
The Caenorhabditis elegans clk-1 gene and the orthologous mouse gene Mclk1 encode a mitochondrial hydroxylase that is necessary for the biosynthesis of ubiquinone (UQ). Mutations in these genes produce broadly pleiotropic phenotypes in both species, including a lengthening of animal lifespan. A number of features of the C. elegans clk-1 mutants, including a maternal effect, particularly extensive pleiotropy, as well as unexplained differences between alleles have suggested that CLK-1/MCLK1 might have additional functions besides that in UQ biosynthesis...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28388876/transcriptomic-buffering-of-cryptic-genetic-variation-contributes-to-meningococcal-virulence
#4
Biju Joseph Ampattu, Laura Hagmann, Chunguang Liang, Marcus Dittrich, Andreas Schlüter, Jochen Blom, Elizaveta Krol, Alexander Goesmann, Anke Becker, Thomas Dandekar, Tobias Müller, Christoph Schoen
BACKGROUND: Commensal bacteria like Neisseria meningitidis sometimes cause serious disease. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous hints towards indispensable virulence factors. Here, in a systems biological approach we compared gene expression of the invasive strain MC58 and the carriage strain α522 under different ex vivo conditions mimicking commensal and virulence compartments to assess the strain-specific impact of gene regulation on meningococcal virulence...
April 7, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28373542/biosynthesis-of-the-pyrrolidine-protein-synthesis-inhibitor-anisomycin-involves-novel-gene-ensemble-and-cryptic-biosynthetic-steps
#5
Xiaoqing Zheng, Qiuxiang Cheng, Fen Yao, Xiaozheng Wang, Lingxin Kong, Bo Cao, Min Xu, Shuangjun Lin, Zixin Deng, Yit-Heng Chooi, Delin You
The protein synthesis inhibitor anisomycin features a unique benzylpyrrolidine system and exhibits diverse biological and pharmacologic activities. Its biosynthetic origin has remained obscure for more than 60 y, however. Here we report the identification of the biosynthetic gene cluster (BGC) of anisomycin in Streptomyces hygrospinosus var. beijingensis by a bioactivity-guided high-throughput screening method. Using a combination of bioinformatic analysis, reverse genetics, chemical analysis, and in vitro biochemical assays, we have identified a core four-gene ensemble responsible for the synthesis of the pyrrolidine system in anisomycin: aniQ, encoding a aminotransferase that catalyzes an initial deamination and a later reamination steps; aniP, encoding a transketolase implicated to bring together an glycolysis intermediate with 4-hydroxyphenylpyruvic acid to form the anisomycin molecular backbone; aniO, encoding a glycosyltransferase that catalyzes a cryptic glycosylation crucial for downstream enzyme processing; and aniN, encoding a bifunctional dehydrogenase that mediates multistep pyrrolidine formation...
April 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28262353/remnants-of-an-ancient-metabolism-without-phosphate
#6
Joshua E Goldford, Hyman Hartman, Temple F Smith, Daniel Segrè
Phosphate is essential for all living systems, serving as a building block of genetic and metabolic machinery. However, it is unclear how phosphate could have assumed these central roles on primordial Earth, given its poor geochemical accessibility. We used systems biology approaches to explore the alternative hypothesis that a protometabolism could have emerged prior to the incorporation of phosphate. Surprisingly, we identified a cryptic phosphate-independent core metabolism producible from simple prebiotic compounds...
March 9, 2017: Cell
https://www.readbyqxmd.com/read/28221784/development-of-a-biosensor-concept-to-detect-the-production-of-cluster-specific-secondary-metabolites
#7
Yi-Qian Sun, Tobias Busche, Christian Rückert, Constanze Paulus, Yuriy Rebets, Renata Novakova, Jörn Kalinowski, Andriy Luzhetskyy, Jan Kormanec, Olga N Sekurova, Sergey B Zotchev
Genome mining of actinomycete bacteria aims at the discovery of novel bioactive secondary metabolites that can be developed into drugs. A new repressor-based biosensor to detect activated secondary metabolite biosynthesis gene clusters in Streptomyces was developed. Biosynthetic gene clusters for undecylprodigiosin and coelimycin in the genome of Streptomyces lividans TK24, which encoded TetR-like repressors and appeared to be almost "silent" based on the RNA-seq data, were chosen for the proof-of-principle studies...
March 3, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28137838/hydroxyl-regioisomerization-of-anthracycline-catalyzed-by-a-four-enzyme-cascade
#8
Zhuan Zhang, Yu-Kang Gong, Qiang Zhou, Yu Hu, Hong-Min Ma, Yong-Sheng Chen, Yasuhiro Igarashi, Lifeng Pan, Gong-Li Tang
Ranking among the most effective anticancer drugs, anthracyclines represent an important family of aromatic polyketides generated by type II polyketide synthases (PKSs). After formation of polyketide cores, the post-PKS tailoring modifications endow the scaffold with various structural diversities and biological activities. Here we demonstrate an unprecedented four-enzyme-participated hydroxyl regioisomerization process involved in the biosynthesis of kosinostatin. First, KstA15 and KstA16 function together to catalyze a cryptic hydroxylation of the 4-hydroxyl-anthraquinone core, yielding a 1,4-dihydroxyl product, which undergoes a chemically challenging asymmetric reduction-dearomatization subsequently acted by KstA11; then, KstA10 catalyzes a region-specific reduction concomitant with dehydration to afford the 1-hydroxyl anthraquinone...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28128554/discovery-of-c-glycosylpyranonaphthoquinones-in-streptomyces-sp-mbt76-by-a-combined-nmr-based-metabolomics-and-bioinformatics-workflow
#9
Changsheng Wu, Chao Du, Koji Ichinose, Young Hae Choi, Gilles P van Wezel
Mining of microbial genomes has revealed that actinomycetes harbor far more biosynthetic potential for bioactive natural products than anticipated. Activation of (cryptic) biosynthetic gene clusters and identification of the corresponding metabolites has become a focal point for drug discovery. Here, we applied NMR-based metabolomics combined with bioinformatics to identify novel C-glycosylpyranonaphthoquinones in Streptomyces sp. MBT76 and to elucidate the biosynthetic pathway. Following activation of the cryptic qin gene cluster for a type II polyketide synthase (PKS) by constitutive expression of its pathway-specific activator, bioinformatics coupled to NMR profiling facilitated the chromatographic isolation and structural elucidation of qinimycins A-C (1-3)...
February 24, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28049346/genoproteomics-assisted-improvement-of-andrographis-paniculata-toward-a-promising-molecular-and-conventional-breeding-platform-for-autogamous-plants-affecting-the-pharmaceutical-industry
#10
Alireza Valdiani, Daryush Talei, Surrinder K Lattoo, Rodomiro Ortiz, Søren Kjærsgaard Rasmussen, Jacqueline Batley, Mohd Yusop Rafii, Mahmood Maziah, Kallevettankuzhy K Sabu, Rambod Abiri, Suchirat Sakuanrungsirikul, Soon Guan Tan
Andrographis paniculata (Burm. f.) Wall. ex Nees. (AP) is a hermaphroditic, self-compatible, and habitual inbreeding plant. Its main bioactive component is andrographolide, which is capable of inducing autophagic cell death in some human cancer cells and helps fight HIV/AIDS. Increasing the andrographolide content by investigating the genetic mechanisms controlling its biosynthesis in order to improve and develop high-yielding cultivars are the main breeding targets for AP. However, there might exist some limitations or barriers for crossability within AP accessions...
January 3, 2017: Critical Reviews in Biotechnology
https://www.readbyqxmd.com/read/28028238/major-transitions-in-dinoflagellate-evolution-unveiled-by-phylotranscriptomics
#11
Jan Janouškovec, Gregory S Gavelis, Fabien Burki, Donna Dinh, Tsvetan R Bachvaroff, Sebastian G Gornik, Kelley J Bright, Behzad Imanian, Suzanne L Strom, Charles F Delwiche, Ross F Waller, Robert A Fensome, Brian S Leander, Forest L Rohwer, Juan F Saldarriaga
Dinoflagellates are key species in marine environments, but they remain poorly understood in part because of their large, complex genomes, unique molecular biology, and unresolved in-group relationships. We created a taxonomically representative dataset of dinoflagellate transcriptomes and used this to infer a strongly supported phylogeny to map major morphological and molecular transitions in dinoflagellate evolution. Our results show an early-branching position of Noctiluca, monophyly of thecate (plate-bearing) dinoflagellates, and paraphyly of athecate ones...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27974049/the-draft-genome-of-whitefly-bemisia-tabaci-meam1-a-global-crop-pest-provides-novel-insights-into-virus-transmission-host-adaptation-and-insecticide-resistance
#12
Wenbo Chen, Daniel K Hasegawa, Navneet Kaur, Adi Kliot, Patricia Valle Pinheiro, Junbo Luan, Marcus C Stensmyr, Yi Zheng, Wenli Liu, Honghe Sun, Yimin Xu, Yuan Luo, Angela Kruse, Xiaowei Yang, Svetlana Kontsedalov, Galina Lebedev, Tonja W Fisher, David R Nelson, Wayne B Hunter, Judith K Brown, Georg Jander, Michelle Cilia, Angela E Douglas, Murad Ghanim, Alvin M Simmons, William M Wintermantel, Kai-Shu Ling, Zhangjun Fei
BACKGROUND: The whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is among the 100 worst invasive species in the world. As one of the most important crop pests and virus vectors, B. tabaci causes substantial crop losses and poses a serious threat to global food security. RESULTS: We report the 615-Mb high-quality genome sequence of B. tabaci Middle East-Asia Minor 1 (MEAM1), the first genome sequence in the Aleyrodidae family, which contains 15,664 protein-coding genes...
December 14, 2016: BMC Biology
https://www.readbyqxmd.com/read/27941800/modulation-of-membrane-phosphoinositide-dynamics-by-the-phosphatidylinositide-4-kinase-activity-of-the-legionella-lepb-effector
#13
Na Dong, Miao Niu, Liyan Hu, Qing Yao, Rui Zhou, Feng Shao
Legionella pneumophila, the causative bacterium for Legionnaires' disease, hijacks host membrane trafficking for the maturation of the Legionella-containing vacuole (LCV). The LCV membrane mainly contains PtdIns4P, which is important for anchoring many secreted Legionella effectors onto the LCV. Here, we identify a cryptic functional domain (LepB_NTD) preceding the well-characterized RabGAP domain in the Legionella Dot/Icm type IV secretion system effector LepB. LepB_NTD alone is toxic to yeast and can disrupt the Golgi in mammalian cells...
December 12, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27866908/biosynthetic-pathway-connects-cryptic-ribosomally-synthesized-posttranslationally-modified-peptide-genes-with-pyrroloquinoline-alkaloids
#14
Peter A Jordan, Bradley S Moore
In an era where natural product biosynthetic gene clusters can be rapidly identified from sequenced genomes, it is unusual for the biosynthesis of an entire natural product class to remain unknown. Yet, the genetic determinates for pyrroloquinoline alkaloid biosynthesis have remained obscure despite their abundance and deceptive structural simplicity. In this work, we have identified the biosynthetic gene cluster for ammosamides A-C, pyrroloquinoline alkaloids from Streptomyces sp. CNR-698. Through direct cloning, heterologous expression and gene deletions we have validated the ammosamide biosynthetic gene cluster and demonstrated that these seemingly simple molecules are derived from a surprisingly complex set of biosynthetic genes that are also found in the biosynthesis of lymphostin, a structurally related pyrroloquinoline alkaloid from Salinispora and Streptomyces...
December 22, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27759375/overexpression-of-the-global-regulator-laea-in-chaetomium-globosum-leads-to-the-biosynthesis-of-chaetoglobosin-z
#15
Tao Jiang, Menghua Wang, Li Li, Jinguang Si, Bo Song, Cao Zhou, Meng Yu, Xuewei Wang, Yonggang Zhang, Gang Ding, Zhongmei Zou
Overexpression of laeA in Chaetomium globosum CBS148.51 up-regulated expression of the chaetoglobosin gene cluster and resulted in the isolation of a new cytochalasan, chaetoglobosin Z (1), together with six known analogues, chaetoglobosins A (2), B (3), D (4), E (5), O (6), and V (7). RT-PCR analysis confirmed that the key genes in the chaetoglobosin gene cluster were significantly up-regulated. The structure of the new compound chaetoglobosin Z (1) was elucidated using NMR data. The relative and absolute configurations were determined by NOESY and electronic circular dichroism combined with quantum-chemical calculations adopting time-dependent density functional theory methods, respectively...
October 28, 2016: Journal of Natural Products
https://www.readbyqxmd.com/read/27732651/metagenomic-analysis-of-the-sponge-discodermia-reveals-the-production-of-the-cyanobacterial-natural-product-kasumigamide-by-entotheonella
#16
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
https://www.readbyqxmd.com/read/27708627/a-phenotypic-and-genotypic-analysis-of-the-antimicrobial-potential-of-cultivable-streptomyces-isolated-from-cave-moonmilk-deposits
#17
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
https://www.readbyqxmd.com/read/27630649/investigating-biochemical-and-developmental-dependencies-of-lignification-with-a-click-compatible-monolignol-analog-in-arabidopsis-thaliana-stems
#18
Jyotsna L Pandey, Sarah N Kiemle, Tom L Richard, Yimin Zhu, Daniel J Cosgrove, Charles T Anderson
Lignin is a key structural component of plant cell walls that provides rigidity, strength, and resistance against microbial attacks. This hydrophobic polymer also serves a crucial role in water transport. Despite its abundance and essential functions, several aspects of lignin biosynthesis and deposition remain cryptic. Lignin precursors are known to be synthesized in the cytoplasm by complex biosynthetic pathways, after which they are transported to the apoplastic space, where they are polymerized via free radical coupling reactions into polymeric lignin...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27618884/new-deferoxamine-glycoconjugates-produced-upon-overexpression-of-pathway-specific-regulatory-gene-in-the-marine-sponge-derived-streptomyces-albus-pva94-07
#19
Olga N Sekurova, Ignacio Pérez-Victoria, Jesús Martín, Kristin F Degnes, Håvard Sletta, Fernando Reyes, Sergey B Zotchev
Activation of silent biosynthetic gene clusters in Streptomyces bacteria via overexpression of cluster-specific regulatory genes is a promising strategy for the discovery of novel bioactive secondary metabolites. This approach was used in an attempt to activate a cryptic gene cluster in a marine sponge-derived Streptomyces albus PVA94-07 presumably governing the biosynthesis of peptide-based secondary metabolites. While no new peptide-based metabolites were detected in the recombinant strain, it was shown to produce at least four new analogues of deferoxamine with additional acyl and sugar moieties, for which chemical structures were fully elucidated...
August 27, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27468291/ascorbate-deficient-vtc2-mutants-in-arabidopsis-do-not-exhibit-decreased-growth
#20
Benson Lim, Nicholas Smirnoff, Christopher S Cobbett, John F Golz
In higher plants the L-galactose pathway represents the major route for ascorbate biosynthesis. The first committed step of this pathway is catalyzed by the enzyme GDP-L-galactose phosphorylase and is encoded by two paralogs in Arabidopsis - VITAMIN C2 (VTC2) and VTC5. The first mutant of this enzyme, vtc2-1, isolated via an EMS mutagenesis screen, has approximately 20-30% of wildtype ascorbate levels and has been reported to have decreased growth under standard laboratory conditions. Here, we show that a T-DNA insertion into the VTC2 causes a similar reduction in ascorbate levels, but does not greatly affect plant growth...
2016: Frontiers in Plant Science
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