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polyketide synthase

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https://www.readbyqxmd.com/read/28633821/enhanced-production-of-hypocrellin-a-by-ultrasound-stimulation-in-submerged-cultures-of-shiraia-bambusicola
#1
Chun Xiao Sun, Yan Jun Ma, Jian Wen Wang
Hypocrellin A (HA), a naturally occurring fungal perylenequinone, is widely used in clinic to treat skin diseases and developed as a photodynamic therapy (PDT) agent against cancers. In this study, a low intensity ultrasound (US, 0.28W/cm(2) at 40kHz) was conducted thrice of repeated US exposure (5-min) with an interval of 12h to stimulate HA production of Shiraia bambusicola after 72h of the initial submerged cultures. US not only increased the content of HA by 177.2% in mycelia, but stimulated the release of HA into the medium with the highest total production of HA (247...
September 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28625788/structural-and-functional-trends-in-dehydrating-bimodules-from-trans-acyltransferase-polyketide-synthases
#2
Drew T Wagner, Jia Zeng, Constance B Bailey, Darren C Gay, Fang Yuan, Hannah R Manion, Adrian T Keatinge-Clay
In an effort to uncover the structural motifs and biosynthetic logic of the relatively uncharacterized trans-acyltransferase polyketide synthases, we have begun the dissection of the enigmatic dehydrating bimodules common in these enzymatic assembly lines. We report the 1.98 Å resolution structure of a ketoreductase (KR) from the first half of a type A dehydrating bimodule and the 2.22 Å resolution structure of a dehydratase (DH) from the second half of a type B dehydrating bimodule. The KR, from the third module of the bacillaene synthase, and the DH, from the tenth module of the difficidin synthase, possess features not observed in structurally characterized homologs...
June 7, 2017: Structure
https://www.readbyqxmd.com/read/28625782/complex-sexual-deception-in-an-orchid-is-achieved-by-co-opting-two-independent-biosynthetic-pathways-for-pollinator-attraction
#3
Haiyang Xu, Björn Bohman, Darren C J Wong, Claudia Rodriguez-Delgado, Adrian Scaffidi, Gavin R Flematti, Ryan D Phillips, Eran Pichersky, Rod Peakall
Sexually deceptive orchids lure their specific male pollinators using volatile semiochemicals that mimic female sex pheromones. To date, the semiochemicals known to be involved consist of blends of chemically and biosynthetically related compounds. In contrast, we report that (S)-β-citronellol and 2-hydroxy-6-methylacetophenone, two biosynthetically distinct compounds, are the active semiochemicals in Caladenia plicata, which is pollinated by male Zeleboria sp. thynnine wasps. They are also sex pheromone components of the female Zeleboria...
June 12, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28618182/mechanism-and-regulation-of-sorbicillin-biosynthesis-by-penicillium-chrysogenum
#4
Fernando Guzmán-Chávez, Oleksandr Salo, Yvonne Nygård, Peter P Lankhorst, Roel A L Bovenberg, Arnold J M Driessen
Penicillium chrysogenum is a filamentous fungus that is used to produce β-lactams at an industrial scale. At an early stage of classical strain improvement, the ability to produce the yellow-coloured sorbicillinoids was lost through mutation. Sorbicillinoids are highly bioactive of great pharmaceutical interest. By repair of a critical mutation in one of the two polyketide synthases in an industrial P. chrysogenum strain, sorbicillinoid production was restored at high levels. Using this strain, the sorbicillin biosynthesis pathway was elucidated through gene deletion, overexpression and metabolite profiling...
June 15, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28608842/talaromyces-marneffei-genomic-transcriptomic-proteomic-and-metabolomic-studies-reveal-mechanisms-for-environmental-adaptations-and-virulence
#5
REVIEW
Susanna K P Lau, Chi-Ching Tsang, Patrick C Y Woo
Talaromycesmarneffei is a thermally dimorphic fungus causing systemic infections in patients positive for HIV or other immunocompromised statuses. Analysis of its ~28.9 Mb draft genome and additional transcriptomic, proteomic and metabolomic studies revealed mechanisms for environmental adaptations and virulence. Meiotic genes and genes for pheromone receptors, enzymes which process pheromones, and proteins involved in pheromone response pathway are present, indicating its possibility as a heterothallic fungus...
June 13, 2017: Toxins
https://www.readbyqxmd.com/read/28605916/identification-and-heterologous-production-of-a-benzoyl-primed-tricarboxylic-acid-polyketide-intermediate-from-the-zaragozic-acid-a-biosynthetic-pathway
#6
Nicholas Liu, Yiu-Sun Hung, Shu-Shan Gao, Leibniz Hang, Yi Zou, Yit-Heng Chooi, Yi Tang
Zaragozic acid A (1) is a potent cholesterol lowering, polyketide natural product made by various filamentous fungi. The reconstitution of enzymes responsible for the initial steps of the biosynthetic pathway of 1 is accomplished using an engineered fungal heterologous host. These initial steps feature the priming of a benzoic acid starter unit onto a highly reducing polyketide synthase (HRPKS), followed by oxaloacetate extension and product release to generate a tricarboxylic acid containing product 2. The reconstitution studies demonstrated that only three enzymes, HRPKS, citrate synthase, and hydrolase, are needed in A...
June 13, 2017: Organic Letters
https://www.readbyqxmd.com/read/28604695/a-scalable-platform-to-identify-fungal-secondary-metabolites-and-their-gene-clusters
#7
Kenneth D Clevenger, Jin Woo Bok, Rosa Ye, Galen P Miley, Maria H Verdan, Thomas Velk, Cynthia Chen, KaHoua Yang, Matthew T Robey, Peng Gao, Matthew Lamprecht, Paul M Thomas, Md Nurul Islam, Jonathan M Palmer, Chengcang C Wu, Nancy P Keller, Neil L Kelleher
The genomes of filamentous fungi contain up to 90 biosynthetic gene clusters (BGCs) encoding diverse secondary metabolites-an enormous reservoir of untapped chemical potential. However, the recalcitrant genetics, cryptic expression, and unculturability of these fungi prevent scientists from systematically exploiting these gene clusters and harvesting their products. As heterologous expression of fungal BGCs is largely limited to the expression of single or partial clusters, we established a scalable process for the expression of large numbers of full-length gene clusters, called FAC-MS...
June 12, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28599654/identification-of-nocamycin-biosynthetic-gene-cluster-from-saccharothrix-syringae-nrrl-b-16468-and-generation-of-new-nocamycin-derivatives-by-manipulating-gene-cluster
#8
Xuhua Mo, Chunrong Shi, Chun Gui, Yanjiao Zhang, Jianhua Ju, Qingji Wang
BACKGROUND: Nocamycins I and II, produced by the rare actinomycete Saccharothrix syringae, belong to the tetramic acid family natural products. Nocamycins show potent antimicrobial activity and they hold great potential for antibacterial agent design. However, up to now, little is known about the exact biosynthetic mechanism of nocamycin. RESULTS: In this report, we identified the gene cluster responsible for nocamycin biosynthesis from S. syringae and generated new nocamycin derivatives by manipulating its gene cluster...
June 9, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28586514/-corrigendum-type%C3%A2-iii-polyketide-synthases-functional-classification-and-phylogenomics
#9
Yugo Shimizu, Hiroyuki Ogata, Susumu Goto
No abstract text is available yet for this article.
June 1, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28583797/penicillospirone-from-a-marine-isolate-of-penicillium-sp-sf-5292-with-anti-inflammatory-activity
#10
Seungjun Lee, Dong-Cheol Kim, Jin-Soo Park, Jae-Young Son, Jae Hak Sohn, Ling Liu, Yongsheng Che, Hyuncheol Oh
Chemical investigation of the EtOAc extract of a marine-derived fungal isolate Penicillium sp. SF-5292 yielded a new polyketide-type metabolite, penicillospirone (1). The structure of 1 was determined by analysis of spectroscopic data such as 1D and 2D NMR spectra and MS data, and the final structure including absolute configuration was unambiguously established by single-crystal X-ray diffraction analysis. In the evaluation of its anti-inflammatory effects, 1 inhibited the overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated RAW264...
May 23, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28570054/directing-the-heterologous-production-of-specific-cyanobacterial-toxin-variants
#11
Tianzhe Liu, Rabia Mazmouz, Sarah E Ongley, Rocky Chau, Russell Pickford, Jason N Woodhouse, Brett A Neilan
Microcystins are globally the most commonly occurring freshwater cyanotoxins, causing acute poisoning and chronically inducing hepatocellular carcinoma. However, the detection and toxicological study of microcystins is hampered by the limited availability and high cost of pure toxin standards. Biosynthesis of microcystin variants in a fast-growing heterologous host offers a promising method of achieving reliable and economically viable alternative to isolating toxin from slow-growing cyanobacterial cultures...
June 7, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28546487/draft-genome-sequence-of-saccharomonospora-sp-strain-lrs4-154-a-moderately-halophilic-actinobacterium-with-the-biotechnologically-relevant-polyketide-synthase-and-nonribosomal-peptide-synthetase-systems
#12
Scarlett Alonso-Carmona, Blanca Vera-Gargallo, Rafael R de la Haba, Antonio Ventosa, Horacio Sandoval-Trujillo, Ninfa Ramírez-Durán
The draft genome sequence of Saccharomonospora sp. strain LRS4.154, a moderately halophilic actinobacterium, has been determined. The genome has 4,860,108 bp, a G+C content of 71.0%, and 4,525 open reading frames (ORFs). The clusters of PKS and NRPS genes, responsible for the biosynthesis of a large number of biomolecules, were identified in the genome.
May 25, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28545544/exploring-the-biocombinatorial-potential-of-benzoxazoles-generation-of-novel-caboxamycin-derivatives
#13
Armando A Losada, Carmen Méndez, José A Salas, Carlos Olano
BACKGROUND: The biosynthesis pathway of benzoxazole compounds caboxamycin and nataxazole have been recently elucidated. Both compounds share one of their precursors, 3-hydroxyanthranilate (two units in the case of nataxazole). In addition, caboxamycin structure includes a salicylate moiety while 6-methylsalycilate is the third scaffold in nataxazole. Pathways cross-talk has been identified in caboxamycin producer Streptomyces sp. NTK937, between caboxamycin and enterobactin pathways, and nataxazole producer Streptomyces sp...
May 25, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28541150/evaluation-of-pathogen-specific-biomarkers-for-the-diagnosis-of-tuberculosis-in-white-tailed-deer-odocoileus-virginianus
#14
Sylvia I Wanzala, Mitchell V Palmer, Wade R Waters, Tyler C Thacker, Michelle Carstensen, Dominic A Travis, Srinand Sreevatsan
OBJECTIVE To develop a noninvasive biomarker-based detection system specific for Mycobacterium bovis for monitoring infection in wild animals. SAMPLE Serum samples from 8 experimentally infected yearling white-tailed deer (Odocoileus virginianus) and 3 age-matched control deer and from 393 Minnesota Department of Natural Resources hunter-harvested white-tailed deer in northwest Minnesota. PROCEDURES 8 yearling deer were inoculated with 2 × 10(8) CFUs of virulent M bovis strain 1315 (day 0), and sera were obtained on days 0, 19, 48, and 60; sera were obtained from 3 uninoculated control deer on those same days...
June 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28534009/genomic-insight-into-mechanisms-of-reversion-of-antibiotic-resistance-in-multidrug-resistant-mycobacterium-tuberculosis-induced-by-a-nanomolecular-iodine-containing-complex-fs-1
#15
Aleksandr I Ilin, Murat E Kulmanov, Ilya S Korotetskiy, Rinat A Islamov, Gulshara K Akhmetova, Marina V Lankina, Oleg N Reva
Drug induced reversion of antibiotic resistance is a promising way to combat multidrug resistant infections. However, lacking knowledge of mechanisms of drug resistance reversion impedes employing this approach in medicinal therapies. Induction of antibiotic resistance reversion by a new anti-tuberculosis drug FS-1 has been reported. FS-1 was used in this work in combination with standard anti-tuberculosis antibiotics in an experiment on laboratory guinea pigs infected with an extensively drug resistant (XDR) strain Mycobacterium tuberculosis SCAID 187...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28529817/coordinated-and-iterative-enzyme-catalysis-in-fungal-polyketide-biosynthesis
#16
Leibniz Hang, Nicholas Liu, Yi Tang
Fungal polyketides are natural products with great chemical diversity that exhibit a wide range of biological activity. This chemical diversity stems from specialized enzymes encoded in the biosynthetic gene cluster responsible for the natural product biosynthesis. Fungal polyketide synthases (PKS) are the megasynthases that produce the carbon scaffolds for the molecules. Subsequent downstream tailoring enzymes such as oxygenases will then further modify the organic framework. In fungi, many of these enzymes have been found to work iteratively-catalyzing multiple reactions on different sites of the substrate...
September 2, 2016: ACS Catalysis
https://www.readbyqxmd.com/read/28528545/discovery-and-biosynthesis-of-gladiolin-a-burkholderia-gladioli-antibiotic-with-promising-activity-against-mycobacterium-tuberculosis
#17
Lijiang Song, Matthew Jenner, Joleen Masschelein, Cerith Jones, Matthew J Bull, Simon R Harris, Ruben C Hartkoorn, Anthony Vocat, Isolda Romero-Canelon, Paul Coupland, Gordon Webster, Matthew Dunn, Rebecca Weiser, Christopher Paisey, Stewart T Cole, Julian Parkhill, Eshwar Mahenthiralingam, Gregory L Challis
An antimicrobial activity screen of Burkholderia gladioli BCC0238, a clinical isolate from a cystic fibrosis patient, led to the discovery of gladiolin, a novel macrolide antibiotic with potent activity against Mycobacterium tuberculosis H37Rv. Gladiolin is structurally related to etnangien, a highly unstable antibiotic from Sorangium cellulosum that is also active against Mycobacteria. Like etnangien, gladiolin was found to inhibit RNA polymerase, a validated drug target in M. tuberculosis. However, gladiolin lacks the highly labile hexaene moiety of etnangien and was thus found to possess significantly increased chemical stability...
June 5, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28525276/chemoenzymatic-total-synthesis-and-structural-diversification-of-tylactone-based-macrolide-antibiotics-through-late-stage-polyketide-assembly-tailoring-and-c-h-functionalization
#18
Andrew N Lowell, Matthew D DeMars, Samuel T Slocum, Fengan Yu, Krithika Anand, Joseph A Chemler, Nisha Korakavi, Jennifer K Priessnitz, Sung Ryeol Park, Aaron A Koch, Pamela J Schultz, David H Sherman
Polyketide synthases (PKSs) represent a powerful catalytic platform capable of effecting multiple carbon-carbon bond forming reactions and oxidation state adjustments. We explored the functionality of two terminal PKS modules that produce the 16-membered tylosin macrocycle, using them as biocatalysts in the chemoenzymatic synthesis of tylactone and its subsequent elaboration to complete the first total synthesis of the juvenimicin, M-4365, and rosamicin classes of macrolide antibiotics via late-stage diversification...
June 5, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28522339/proteomics-analysis-of-fusarium-proliferatum-under-various-initial-ph-during-fumonisin-production
#19
Taotao Li, Liang Gong, Yong Wang, Feng Chen, Vijai Kumar Gupta, Qijie Jian, Xuewu Duan, Yueming Jiang
Fusarium proliferatum as a fungal pathogen can produce fumonisin which causes a great threat to animal and human health. Proteomic approach was a useful tool for investigation into mycotoxin biosynthesis in fungal pathogens. In this study, we analyzed the fumonisin content and mycelium proteins of Fusarium proliferatum cultivated under the initial pH5 and 10. Fumonisin production after 10days was significantly induced in culture condition at pH10 than pH5. Ninety nine significantly differently accumulated protein spots under the two pH conditions were detected using two dimensional polyacrylamide gel electrophoresis and 89 of these proteins were successfully identified by MALDI-TOF/TOF and LC-ESI-MS/MS analysis...
May 15, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28517364/a-cryptic-pigment-biosynthetic-pathway-uncovered-by-heterologous-expression-is-essential-for-conidial-development-in-pestalotiopsis-fici
#20
Peng Zhang, Xiuna Wang, Aili Fan, Yanjing Zheng, Xingzhong Liu, Shihua Wang, Huixi Zou, Berl R Oakley, Nancy P Keller, Wen-Bing Yin
Spore pigmentation is very common in the fungal kingdom. The best studied pigment in fungi is melanin which coats the surface of single cell spores. What and how pigments function in a fungal species with multiple cell conidia is poorly understood. Here, we identified and deleted a polyketide synthase (PKS) gene PfmaE and showed that it is essential for multicellular conidial pigmentation and development in a plant endophytic fungus, Pestalotiopsis fici. To further characterize the melanin pathway, we utilized an advanced Aspergillus nidulans heterologous system for the expression of the PKS PfmaE and the Pfma gene cluster...
May 18, 2017: Molecular Microbiology
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