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Rolf Müller - One of the best experts on this subject based on the ideXlab platform.
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Heterologous Expression of bacterial natural product biosynthetic pathways
Natural Product Reports, 2019Co-Authors: Liujie Huo, Xiaoying Bian, Youming Zhang, Joachim J Hug, Rolf MüllerAbstract:Covering: 2013 to June 2018 Heterologous Expression of natural product biosynthetic pathways is of increasing interest in microbial biotechnology, drug discovery and optimization. It empowers not only the robust production of valuable biomolecules in more amenable Heterologous hosts but also permits the generation of novel analogs through biosynthetic engineering. This strategy also facilitates the discovery of novel bioactive compounds following the functional Expression of cryptic biosynthetic gene clusters (BGCs) from fastidious original producers or metagenomic DNA in surrogate hosts, thus facilitating genome mining in the post-genomic era. This review discusses recent advances and trends pertaining to the Heterologous production of bacterial natural products, with an emphasis on new techniques, Heterologous hosts, and novel chemistry since 2013.
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Recent advances in the Heterologous Expression of microbial natural product biosynthetic pathways.
Natural product reports, 2013Co-Authors: Sarah E. Ongley, Xiaoying Bian, Brett A. Neilan, Rolf MüllerAbstract:Covering: up to 2013The Heterologous Expression of microbial natural product biosynthetic pathways coupled with advanced DNA engineering enables optimisation of product yields, functional elucidation of cryptic gene clusters, and generation of novel derivatives. This review summarises the recent advances in cloning and maintenance of natural product biosynthetic gene clusters for Heterologous Expression and the efforts fundamental for discovering novel natural products in the post-genomics era, with a focus on polyketide synthases (PKSs) and non-ribosomal polypeptide synthetases (NRPS).
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Heterologous Expression and genetic engineering of the tubulysin biosynthetic gene cluster using red et recombineering and inactivation mutagenesis
Chemistry & Biology, 2012Co-Authors: Yi Chai, Shiping Shan, Kira J Weissman, Shengbiao Hu, Youming Zhang, Rolf MüllerAbstract:Summary Although the tubulysin (tub) biosynthetic gene cluster has been located in two myxobacterial strains, it appears in both cases to be incomplete as obvious candidates for acyl transfer and oxidation functions are lacking. Here, we report the engineering of a Heterologous Expression system for the tub biosynthetic pathway from strain C ystobacter sp. SBCb004. The entire tub core cluster was reconstituted from two cosmids using Red/ET recombineering and Heterologous Expression achieved in strains Pseudomonas putida and Myxococcus xanthus . Availability of the Heterologous Expression system and the natural producer strain SBCb004 provided a platform for the functional investigation of various biosynthetic genes by targeted inactivation. In addition, BLAST analysis of SBCb004 genome data was used to identify multiple candidate monooxygenases, whose involvement in tubulysin assembly was evaluated using a combination of knockout mutagenesis and Heterologous Expression.
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Heterologous Expression and Genetic Engineering of the Tubulysin Biosynthetic Gene Cluster Using Red/ET Recombineering and Inactivation Mutagenesis
Chemistry & biology, 2012Co-Authors: Yi Chai, Shiping Shan, Kira J Weissman, Youming Zhang, Rolf MüllerAbstract:Summary Although the tubulysin (tub) biosynthetic gene cluster has been located in two myxobacterial strains, it appears in both cases to be incomplete as obvious candidates for acyl transfer and oxidation functions are lacking. Here, we report the engineering of a Heterologous Expression system for the tub biosynthetic pathway from strain C ystobacter sp. SBCb004. The entire tub core cluster was reconstituted from two cosmids using Red/ET recombineering and Heterologous Expression achieved in strains Pseudomonas putida and Myxococcus xanthus . Availability of the Heterologous Expression system and the natural producer strain SBCb004 provided a platform for the functional investigation of various biosynthetic genes by targeted inactivation. In addition, BLAST analysis of SBCb004 genome data was used to identify multiple candidate monooxygenases, whose involvement in tubulysin assembly was evaluated using a combination of knockout mutagenesis and Heterologous Expression.
Haruo Ikeda - One of the best experts on this subject based on the ideXlab platform.
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Comprehensive Derivatization of Thioviridamides by Heterologous Expression.
ACS chemical biology, 2019Co-Authors: Kei Kudo, Noritaka Kagaya, Hanae Koiwai, Makoto Nishiyama, Tomohisa Kuzuyama, Kazuo Shin-ya, Haruo IkedaAbstract:New technology for the derivatization of peptide natural products is required for drug development. Despite the recent advances in the genome sequencing technique enabling us to search for the biosynthetic genes for wide variety of natural products, the technical methods to get access to them are limited. A class of RiPPs, a recently emerged natural product family such as thioviridamide, is one of those possessing such unexplored chemical space. In this paper, we report a streamlined method to generate new thioviridamide derivatives and to assess their biological activities. Heterologous Expression of 42 constructs in an engineered Streptomyces avermitilis host gave 35 designed thioviridamide derivatives, along with several unprecedented analogues. Moreover, cytotoxicity assay revealed that several derivatives showed more potent activities than those of prethioviridamide. These results indicate that this strategy can become one of the potential ways to produce supreme unnatural products.
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Novel macrolactam compound produced by the Heterologous Expression of a large cryptic biosynthetic gene cluster of Streptomyces rochei IFO12908
'Springer Science and Business Media LLC', 2019Co-Authors: Takuya Hashimoto, Ikuko Kozone, Junko Hashimoto, Noritaka Kagaya, Manabu Fujie, Haruo Ikeda, Noriyuki Sato, Reiko Ueoka, Kazuo Shin-yaAbstract:In the course of our studies on the Heterologous Expression of giant biosynthetic genes, we discovered a novel cryptic biosynthetic gene cluster in Streptomyces rochei IFO12908. During our efforts to express biosynthetic genes using the host SUKA strain derived from Streptomyces avermitilis, a novel polyene macrolactam compound designated as JBIR-156 was produced. We report herein the cloning and Heterologous Expression of the JBIR-156 biosynthetic gene cluster, and the isolation, structure determination, and cytotoxic activity of this novel compound
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neothioviridamide a polythioamide compound produced by Heterologous Expression of a streptomyces sp cryptic ripp biosynthetic gene cluster
Journal of Natural Products, 2018Co-Authors: Teppei Kawahara, Miho Izumikawa, Ikuko Kozone, Junko Hashimoto, Noritaka Kagaya, Hanae Koiwai, Mamoru Komatsu, Manabu Fujie, Noriyuki Sato, Haruo IkedaAbstract:During genome mining for thioviridamide-like biosynthetic gene clusters that could produce polythioamide RiPP (ribosomally synthesized and post-translationally modified peptides), we discovered a novel cryptic biosynthetic gene cluster. During efforts to express this biosynthetic gene using Heterologous Expression of this biosynthetic gene cluster, a novel compound designated as neothioviridamide was produced. We report herein the cloning and Heterologous Expression of the neothioviridamide biosynthetic gene cluster and the isolation, structure determination, and cytotoxic activity of neothioviridamide.
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Novel terpenes generated by Heterologous Expression of bacterial terpene synthase genes in an engineered Streptomyces host
The Journal of Antibiotics, 2015Co-Authors: Yuuki Yamada, Kazuo Shin-ya, Shiho Arima, Tohru Nagamitsu, Kohei Johmoto, Hidehiro Uekusa, Tadashi Eguchi, David E Cane, Haruo IkedaAbstract:Mining of bacterial genome data has revealed numerous presumptive terpene synthases. Heterologous Expression of several putative terpene synthase genes in an engineered Streptomyces host has revealed 13 newly discovered terpenes whose GC-MS and NMR data did not match with any known compounds in spectroscopic databases. Each of the genes encoding the corresponding terpene synthases were silent in their parent microorganisms. Heterologous Expression and detailed NMR spectroscopic analysis allowed assignment of the structures of 13 new cyclic terpenes. Among these newly identified compounds, two were found to be linear triquinane sesquiterpenes that have never previously been isolated from bacteria or any other source. The remaining 11 new compounds were shown to be diterpene hydrocarbons and alcohol, including hydropyrene ( 1 ), hydropyrenol ( 2 ), tsukubadiene ( 11 ) and odyverdienes A ( 12 ) and B ( 13 ) each displaying a novel diterpene skeleton that had not previously been reported.
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Novel thioviridamide derivative--JBIR-140: Heterologous Expression of the gene cluster for thioviridamide biosynthesis.
The Journal of antibiotics, 2015Co-Authors: Miho Izumikawa, Ikuko Kozone, Junko Hashimoto, Noritaka Kagaya, Motoki Takagi, Hanae Koiwai, Mamoru Komatsu, Manabu Fujie, Noriyuki Satoh, Haruo IkedaAbstract:Novel thioviridamide derivative—JBIR-140: Heterologous Expression of the gene cluster for thioviridamide biosynthesis
Youming Zhang - One of the best experts on this subject based on the ideXlab platform.
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Heterologous Expression of bacterial natural product biosynthetic pathways
Natural Product Reports, 2019Co-Authors: Liujie Huo, Xiaoying Bian, Youming Zhang, Joachim J Hug, Rolf MüllerAbstract:Covering: 2013 to June 2018 Heterologous Expression of natural product biosynthetic pathways is of increasing interest in microbial biotechnology, drug discovery and optimization. It empowers not only the robust production of valuable biomolecules in more amenable Heterologous hosts but also permits the generation of novel analogs through biosynthetic engineering. This strategy also facilitates the discovery of novel bioactive compounds following the functional Expression of cryptic biosynthetic gene clusters (BGCs) from fastidious original producers or metagenomic DNA in surrogate hosts, thus facilitating genome mining in the post-genomic era. This review discusses recent advances and trends pertaining to the Heterologous production of bacterial natural products, with an emphasis on new techniques, Heterologous hosts, and novel chemistry since 2013.
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Heterologous Expression and genetic engineering of the tubulysin biosynthetic gene cluster using red et recombineering and inactivation mutagenesis
Chemistry & Biology, 2012Co-Authors: Yi Chai, Shiping Shan, Kira J Weissman, Shengbiao Hu, Youming Zhang, Rolf MüllerAbstract:Summary Although the tubulysin (tub) biosynthetic gene cluster has been located in two myxobacterial strains, it appears in both cases to be incomplete as obvious candidates for acyl transfer and oxidation functions are lacking. Here, we report the engineering of a Heterologous Expression system for the tub biosynthetic pathway from strain C ystobacter sp. SBCb004. The entire tub core cluster was reconstituted from two cosmids using Red/ET recombineering and Heterologous Expression achieved in strains Pseudomonas putida and Myxococcus xanthus . Availability of the Heterologous Expression system and the natural producer strain SBCb004 provided a platform for the functional investigation of various biosynthetic genes by targeted inactivation. In addition, BLAST analysis of SBCb004 genome data was used to identify multiple candidate monooxygenases, whose involvement in tubulysin assembly was evaluated using a combination of knockout mutagenesis and Heterologous Expression.
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Heterologous Expression and Genetic Engineering of the Tubulysin Biosynthetic Gene Cluster Using Red/ET Recombineering and Inactivation Mutagenesis
Chemistry & biology, 2012Co-Authors: Yi Chai, Shiping Shan, Kira J Weissman, Youming Zhang, Rolf MüllerAbstract:Summary Although the tubulysin (tub) biosynthetic gene cluster has been located in two myxobacterial strains, it appears in both cases to be incomplete as obvious candidates for acyl transfer and oxidation functions are lacking. Here, we report the engineering of a Heterologous Expression system for the tub biosynthetic pathway from strain C ystobacter sp. SBCb004. The entire tub core cluster was reconstituted from two cosmids using Red/ET recombineering and Heterologous Expression achieved in strains Pseudomonas putida and Myxococcus xanthus . Availability of the Heterologous Expression system and the natural producer strain SBCb004 provided a platform for the functional investigation of various biosynthetic genes by targeted inactivation. In addition, BLAST analysis of SBCb004 genome data was used to identify multiple candidate monooxygenases, whose involvement in tubulysin assembly was evaluated using a combination of knockout mutagenesis and Heterologous Expression.
Neil S. Millar - One of the best experts on this subject based on the ideXlab platform.
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Characterisation of insect nicotinic acetylcholine receptors by Heterologous Expression.
Advances in experimental medicine and biology, 2010Co-Authors: Neil S. Millar, Stuart J. LansdellAbstract:As with other neurotransmitter receptors and ion channels, characterisation of nicotinic acetylcholine receptors (nAChRs) has relied heavily on studies conducted with cloned receptors expressed in artificial Expression systems. Although much has been achieved in recent years by such studies, considerable problems have been encountered in the Heterologous Expression of several nAChR subtypes; problems that have been particularly pronounced for insect nAChRs. Here we will review studies that have been conducted with nAChRs cloned from insects, with emphasis on experimental strategies that have been employed in an attempt to circumvent the problems associated with inefficient Heterologous Expression of insect nAChRs. These approaches include the Expression of hybrid nAChRs (containing insect nAChR subunit co-expressed with vertebrate subunits), artificial subunit chimeras and the co-Expression of molecular chaperones such as RIC-3.
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A review of experimental techniques used for the Heterologous Expression of nicotinic acetylcholine receptors
Biochemical Pharmacology, 2009Co-Authors: Neil S. MillarAbstract:Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop family of neurotransmitter-gated ion channels, a family that also includes receptors for γ-aminobutyric acid, glycine and 5-hydroxytryptamine. In humans, nAChRs have been implicated in several neurological and psychiatric disorders and are major targets for pharmaceutical drug discovery. In addition, nAChRs are important targets for neuroactive pesticides in insects and in other invertebrates. Historically, nAChRs have been one of the most intensively studied families of neurotransmitter receptors. They were the first neurotransmitter receptors to be biochemically purified and the first to be characterized by molecular cloning and Heterologous Expression. Although much has been learnt from studies of native nAChRs, the Expression of recombinant nAChRs has provided dramatic advances in the characterization of these important receptors. This review will provide a brief history of the characterization of nAChRs by Heterologous Expression. It will focus, in particular, upon studies of recombinant nAChRs, work that has been conducted by many hundreds of scientists during a period of almost 30 years since the molecular cloning of nAChR subunits in the early 1980s. © 2009.
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Dbeta3, an atypical nicotinic acetylcholine receptor subunit from Drosophila : molecular cloning, Heterologous Expression and coassembly.
Journal of neurochemistry, 2002Co-Authors: Stuart J. Lansdell, Neil S. MillarAbstract:Insect nicotinic acetylcholine receptors (nAChRs) play a central role in mediating neuronal synaptic transmission and are the target sites for the increasingly important group of neonicotinoid insecticides. Six nicotinic acetylcholine receptor (nAChR) subunits (four alpha-type and two beta-type) have been cloned previously from the model insect species Drosophila melanogaster. Despite extensive efforts, it has not been possible to generate functional recombinant nAChRs by Heterologous Expression of any combination of these six subunits. It has, however, been possible to express functional hybrid receptors when Drosophila alpha subunits are co-expressed with vertebrate beta subunits. This has led to the assumption that successful Heterologous Expression might require an, as yet, uncloned beta-type insect subunit. Examination of the recently completed Drosophila genomic sequence data has identified a novel putative nAChR beta-type subunit. Here we report the molecular cloning, Heterologous Expression and characterization of this putative Drosophila nAChR subunit (Dbeta3). Phylogenetic comparisons with other ligand-gated ion channel subunit sequences support its classification as a nAChR subunit but show it to be a distantly related member of this neurotransmitter receptor subunit family. Evidence that the Dbeta3 subunit is able to coassemble with other Drosophila nAChR subunits and contribute to recombinant nAChRs has been obtained by both radioligand binding and coimmunoprecipitation studies in transfected Drosophila S2 cells.
Shiping Shan - One of the best experts on this subject based on the ideXlab platform.
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Heterologous Expression and genetic engineering of the tubulysin biosynthetic gene cluster using red et recombineering and inactivation mutagenesis
Chemistry & Biology, 2012Co-Authors: Yi Chai, Shiping Shan, Kira J Weissman, Shengbiao Hu, Youming Zhang, Rolf MüllerAbstract:Summary Although the tubulysin (tub) biosynthetic gene cluster has been located in two myxobacterial strains, it appears in both cases to be incomplete as obvious candidates for acyl transfer and oxidation functions are lacking. Here, we report the engineering of a Heterologous Expression system for the tub biosynthetic pathway from strain C ystobacter sp. SBCb004. The entire tub core cluster was reconstituted from two cosmids using Red/ET recombineering and Heterologous Expression achieved in strains Pseudomonas putida and Myxococcus xanthus . Availability of the Heterologous Expression system and the natural producer strain SBCb004 provided a platform for the functional investigation of various biosynthetic genes by targeted inactivation. In addition, BLAST analysis of SBCb004 genome data was used to identify multiple candidate monooxygenases, whose involvement in tubulysin assembly was evaluated using a combination of knockout mutagenesis and Heterologous Expression.
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Heterologous Expression and Genetic Engineering of the Tubulysin Biosynthetic Gene Cluster Using Red/ET Recombineering and Inactivation Mutagenesis
Chemistry & biology, 2012Co-Authors: Yi Chai, Shiping Shan, Kira J Weissman, Youming Zhang, Rolf MüllerAbstract:Summary Although the tubulysin (tub) biosynthetic gene cluster has been located in two myxobacterial strains, it appears in both cases to be incomplete as obvious candidates for acyl transfer and oxidation functions are lacking. Here, we report the engineering of a Heterologous Expression system for the tub biosynthetic pathway from strain C ystobacter sp. SBCb004. The entire tub core cluster was reconstituted from two cosmids using Red/ET recombineering and Heterologous Expression achieved in strains Pseudomonas putida and Myxococcus xanthus . Availability of the Heterologous Expression system and the natural producer strain SBCb004 provided a platform for the functional investigation of various biosynthetic genes by targeted inactivation. In addition, BLAST analysis of SBCb004 genome data was used to identify multiple candidate monooxygenases, whose involvement in tubulysin assembly was evaluated using a combination of knockout mutagenesis and Heterologous Expression.