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David A Hopwood - One of the best experts on this subject based on the ideXlab platform.
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β ketoacyl acyl carrier protein synthase iii fabh is essential for fatty acid biosynthesis in Streptomyces Coelicolor a3 2
Journal of Bacteriology, 2001Co-Authors: Peter W Revill, Maureen J. Bibb, Annkarolin Scheu, Helen J Kieser, David A HopwoodAbstract:The Streptomyces Coelicolor fab (fatty acid biosynthesis) gene cluster (fabD-fabH-acpP-fabF) is cotranscribed to produce a leaderless mRNA transcript. One of these genes, fabH, encodes a ketoacyl synthase III that is essential to and is proposed to be responsible for initiation of fatty acid biosynthesis in S. Coelicolor.
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functional complementation of pyran ring formation in actinorhodin biosynthesis in Streptomyces Coelicolor a3 2 by ketoreductase genes for granaticin biosynthesis
Journal of Bacteriology, 2001Co-Authors: Koji Ichinose, Takaaki Taguchi, Yutaka Ebizuka, David J. Bedford, David A HopwoodAbstract:A mutation in actVI-ORF1, which controls C-3 reduction in actinorhodin biosynthesis by Streptomyces Coelicolor, was complemented by gra-ORF5 and -ORF6 from the granaticin biosynthetic gene cluster of Streptomyces violaceoruber Tu22. It is hypothesized that, while gra-ORF5 alone is a ketoreductase for C-9, gra-ORF6 gives the enzyme regiospecificity also for C-3.
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proof that the actvi genetic region of Streptomyces Coelicolor a3 2 is involved in stereospecific pyran ring formation in the biosynthesis of actinorhodin
Bioorganic & Medicinal Chemistry Letters, 1999Co-Authors: Koji Ichinose, Chandres Surti, Takaaki Taguchi, Kevin I Bookermilburm, Yutaka Ebizuka, Richard G Stephenson, Francisco Malpartida, David A HopwoodAbstract:Pyran ring formation in the biosynthesis of actinorhodin in Streptomyces Coelicolor A3(2) was studied using the act cluster deficient strain, CH999, carrying pRM5-based plasmids harbouring combinations of the actVI genes. The strain, CH999/pIJ5660 (pRM5 + actVI-ORF1), produced a chiral intermediate, (S)-DNPA, suggesting that the actVI-ORF1 product is a reductase determining the C-3 stereochemical centre.
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physical identification of a chromosomal locus encoding biosynthetic genes for the lipopeptide calcium dependent antibiotic cda of Streptomyces Coelicolor a3 2
Microbiology, 1998Co-Authors: Pei Pei Chong, David A Hopwood, Sylvia M Podmore, Helen M Kieser, Matthias Redenbach, Kursad Turgay, Mohamed A Marahiel, Colin P. SmithAbstract:Summary: Putative peptide-synthetase-encoding DNA fragments were isolated from the Streptomyces Coelicolor A3(2) chromosome using a PCR-based approach and mapped to a single ∼ 35 kb segment. In integrative transformation experiments, DNA fragments from this region disrupted production of the calcium-dependent antibiotic (CDA) and had sequences characteristic of non-ribosomal peptide synthetases, thus proving that the cda locus had been cloned.
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Production of Actinorhodin-Related ‘‘Blue Pigments’’ by Streptomyces Coelicolor A3(2)
1996Co-Authors: Leonid Bystrykh, Francisco Malpartida, David A Hopwood, Miguel Ángel Fernández-moreno, J. K. Herrema, Lubbert DijkhuizenAbstract:The genetically well-known strain Streptomyces Coelicolor A3(2) produces the pH indicator (red/blue) antibiotic actinorhodin, but not all the ‘‘blue pigment’’ produced by this strain is actinorhodin. When the organism was subjected to various nutrient limitations (ammonium, nitrate, phosphate, or trace elements), and also during growth cessation caused by a relatively low medium pH, blue pigment production was initiated but the pigment and its location varied. At pH 4.5 to 5.5, significant formation of actinorhodin occurred and was located exclusively intracellularly. At pH 6.0 to 7.5 a different blue pigment was produced intracellularly as well as extracellularly. It was purified and identified as γ-actinorhodin (the lactone form of actinorhodin). Analysis of act mutants of S. Coelicolor A3(2) confirmed that both pigments are derived from the act biosynthetic pathway. Mutants with lesions in actII-ORF2, actII-ORF3, or actVA-ORF1, previously implicated or suggested to be involved in actinorhodin export, were impaired in production of γ-actinorhodin, suggesting that synthesis of γ-actinorhodin from actinorhodin is coupled to its export from the cell. However, effects on the level of actinorhodin production were also found in some mutants.
Gregory L Challis - One of the best experts on this subject based on the ideXlab platform.
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discovery of a new peptide natural product by Streptomyces Coelicolor genome mining
Nature Chemical Biology, 2005Co-Authors: Sylvie Lautru, Robert J Deeth, Lianne M Bailey, Gregory L ChallisAbstract:Analyses of microbial genome sequences reveal numerous examples of gene clusters encoding proteins typically involved in complex natural product biosynthesis but not associated with the production of known natural products. In Streptomyces Coelicolor M145 there are several gene clusters encoding new nonribosomal peptide synthetase (NRPS) systems not associated with known metabolites. Application of structure-based models for substrate recognition by NRPS adenylation domains predicts the amino acids incorporated into the putative peptide products of these systems, but the accuracy of these predictions is untested. Here we report the isolation and structure determination of the new tris-hydroxamate tetrapeptide iron chelator coelichelin from S. Coelicolor using a genome mining approach guided by substrate predictions for the trimodular NRPS CchH, and we show that this enzyme, which lacks a C-terminal thioesterase domain, together with a homolog of enterobactin esterase (CchJ), are required for coelichelin biosynthesis. These results demonstrate that accurate prediction of adenylation domain substrate selectivity is possible and raise intriguing mechanistic questions regarding the assembly of a tetrapeptide by a trimodular NRPS.
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identification of a cluster of genes that directs desferrioxamine biosynthesis in Streptomyces Coelicolor m145
Journal of the American Chemical Society, 2004Co-Authors: Francisco Baronagomez, Ursula Wong, Anastassios E Giannakopulos, Peter J. Derrick, Gregory L ChallisAbstract:Desferrioxamines are a structurally related family of tris-hydroxamate siderophores that form strong hexadentate complexes with ferric iron. Desferrioxamine B has been used clinically for the treatment of iron overload in man. We have unambiguously identified desferrioxamine E as the major desferrioxamine siderophore produced by Streptomyces Coelicolor M145 and have identified a cluster of four genes (desA−D) that directs desferrioxamine biosynthesis in this model actinomycete. On the basis of comparative sequence analysis of the proteins encoded by these genes, we propose a plausible pathway for desferrioxamine biosynthesis. The desferrioxamine biosynthetic pathway belongs to a new and rapidly emerging family of pathways for siderophore biosynthesis, widely distributed across diverse species of bacteria, which is biochemically distinct from the better known nonribosomal peptide synthetase (NRPS) pathway used in many organisms for siderophore biosynthesis.
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complete genome sequence of the model actinomycete Streptomyces Coelicolor a3 2
Nature, 2002Co-Authors: Stephen D Bentley, Gregory L Challis, Keith F. Chater, Ana Cerdenotarraga, Nicholas R Thomson, Keith D James, David Harris, Michael A Quail, H M KieserAbstract:Streptomyces Coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.
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coelichelin a new peptide siderophore encoded by the Streptomyces Coelicolor genome structure prediction from the sequence of its non ribosomal peptide synthetase
Fems Microbiology Letters, 2000Co-Authors: Gregory L Challis, Jacques RavelAbstract:A gene cluster for the non-ribosomal synthesis of a peptide of unknown structure has been identified in the partial genome sequence of Streptomyces Coelicolor. Using molecular and computational analyses, the total structure of a tripeptide siderophore synthesized by the non-ribosomal peptide synthetase within the cluster has been deduced from the translated sequence of its encoding gene. This represents a novel method for the structural assignment of natural products from genome sequence data.
Mervyn J. Bibb - One of the best experts on this subject based on the ideXlab platform.
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heterologous expression of natural product biosynthetic gene clusters in Streptomyces Coelicolor from genome mining to manipulation of biosynthetic pathways
Journal of Industrial Microbiology & Biotechnology, 2014Co-Authors: Juan Pablo Gomezescribano, Mervyn J. BibbAbstract:Heterologous gene expression is one of the main strategies used to access the full biosynthetic potential of actinomycetes, as well as to study the metabolic pathways of natural product biosynthesis and to create unnatural pathways. Streptomyces Coelicolor A3(2) is the most studied member of the actinomycetes, bacteria renowned for their prolific capacity to synthesize a wide range of biologically active specialized metabolites. We review here the use of strains of this species for the heterologous production of structurally diverse actinomycete natural products.
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Engineering Streptomyces Coelicolor for heterologous expression of secondary metabolite gene clusters
Microbial biotechnology, 2010Co-Authors: Juan Pablo Gomez-escribano, Mervyn J. BibbAbstract:We have constructed derivatives of Streptomyces Coelicolor M145 as hosts for the heterologous expression of secondary metabolite gene clusters. To remove potentially competitive sinks of carbon and nitrogen, and to provide a host devoid of antibiotic activity, we deleted four endogenous secondary metabolite gene clusters from S. Coelicolor M145 – those for actinorhodin, prodiginine, CPK and CDA biosynthesis. We then introduced point mutations into rpoB and rpsL to pleiotropically increase the level of secondary metabolite production. Introduction of the native actinorhodin gene cluster and of gene clusters for the heterologous production of chloramphenicol and congocidine revealed dramatic increases in antibiotic production compared with the parental strain. In addition to lacking antibacterial activity, the engineered strains possess relatively simple extracellular metabolite profiles. When combined with liquid chromatography and mass spectrometry, we believe that these genetically engineered strains will markedly facilitate the discovery of new compounds by heterologous expression of cloned gene clusters, particularly the numerous cryptic secondary metabolic gene clusters that are prevalent within actinomycete genome sequences.
Stanley N Cohen - One of the best experts on this subject based on the ideXlab platform.
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putative tetr family transcriptional regulator sco1712 encodes an antibiotic downregulator in Streptomyces Coelicolor
Applied and Environmental Microbiology, 2010Co-Authors: Hanna Lee, Jianqiang Huang, Stanley N Cohen, Seonhye Kim, Junhee Noh, Eungsoo KimAbstract:A tetR family transcriptional regulatory gene (SCO1712) was identified as a global antibiotic regulatory gene from a Streptomyces interspecies DNA microarray analysis. SCO1712 disruption in Streptomyces Coelicolor not only upregulated antibiotic biosynthesis through pathway-specific regulators when a previously identified pleiotropic downregulatory wblA was expressed but also further stimulated antibiotic production in a wblA deletion mutant, implying that SCO1712 might encode a novel antibiotic downregulator.
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regional organization of gene expression in Streptomyces Coelicolor
Gene, 2005Co-Authors: Nitsara Karoonuthaisiri, Jianqiang Huang, David Weaver, Stanley N CohenAbstract:Abstract Based on the chromosomal locations of genes inferred from sequence analysis to be essential for the viability of Streptomyces Coelicolor , Bentley et al. [Bentley, S.D., et al. 2002. Complete genome sequence of the model actinomycete Streptomyces Coelicolor A3(2), Nature 417, 141–147.] have suggested that a 4.9 Mb central region of the linear S. Coelicolor chromosome encodes ‘core’ functions expressed during vegetative growth of this species, while 1.5 Mb and 2.3 Mb chromosomal DNA segments lateral to this core encode auxiliary functions proposed to be required under other growth conditions. To examine this hypothesis and experimentally identify genes expressed during vegetative growth of S. Coelicolor cultures, we used DNA microarrays to measure globally the abundance of S. Coelicolor transcripts in cells growing in liquid medium. We found that, overall, genes corresponding to the 4.9 Mb core region of the S. Coelicolor M145 chromosome were more highly expressed under non-limiting growth conditions than genes in the 1.5 Mb left and 2.3 Mb right chromosome arms, supporting the notion of the core versus auxiliary organization of genes on the chromosome. To examine how this chromosomal distribution of transcripts changes under other growth conditions, we also measured gene expression changes during stationary phase and several stress conditions. During stationary phase, the composition of S. Coelicolor transcripts appears to shift from large quantities of growth-related transcripts encoded in the core region to those of less characterized genes, which may be essential for differentiation and other physiological responses, encoded throughout the chromosome. After temperature and osmotic upshifts, we found that S. Coelicolor transiently induces a set of several hundred genes located throughout the chromosome, which may function in response mechanisms common to the two stress conditions.
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The Streptomyces Coelicolor Polynucleotide Phosphorylase Homologue, and Not the Putative Poly(A) Polymerase, Can Polyadenylate RNA
Journal of Bacteriology, 2003Co-Authors: Björn Sohlberg, Jianqiang Huang, Stanley N CohenAbstract:A protein containing a nucleotidyltransferase motif characteristic of poly(A) polymerases has been proposed to polyadenylate RNA in Streptomyces Coelicolor (P. Bralley and G. H. Jones, Mol. Microbiol. 40: 1155-1164, 2001). We show that this protein lacks poly(A) polymerase activity and is instead a tRNA nucleotidyltransferase that repairs CCA ends of tRNAs. In contrast, a Streptomyces Coelicolor polynucleotide phosphorylase homologue that exhibits polyadenylation activity may account for the poly(A) tails found in this organism.
Koji Ichinose - One of the best experts on this subject based on the ideXlab platform.
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identification of the actinorhodin monomer and its related compound from a deletion mutant of the actva orf4 gene of Streptomyces Coelicolor a3 2
Bioorganic & Medicinal Chemistry Letters, 2012Co-Authors: Takaaki Taguchi, Susumu Okamoto, Takayuki Ebihara, Atsushi Furukawa, Yumiko Hidaka, Ryuji Ariga, Koji IchinoseAbstract:An oxygenated derivative of dihydrokalafungin (DHK) was isolated from a deletion mutant of the actVA-ORF4 gene involved in the biosynthesis of a dimeric benzoisochromanequinone (BIQ) antibiotic, actinorhodin (ACT), in Streptomyces Coelicolor A3(2). Spectroscopic analysis elucidated its structure as 8-hydroxy-DHK, corresponding to the monomeric unit of ACT. Further metabolite analysis identified its related compound, clearly derived from the reduction of 8-hydroxy-DHK. The structures of these metabolites indicate the essential role of ActVA-ORF4 in ACT biosynthesis, specifically in dimerization of a BIQ intermediate via C-C bond formation.
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functional complementation of pyran ring formation in actinorhodin biosynthesis in Streptomyces Coelicolor a3 2 by ketoreductase genes for granaticin biosynthesis
Journal of Bacteriology, 2001Co-Authors: Koji Ichinose, Takaaki Taguchi, Yutaka Ebizuka, David J. Bedford, David A HopwoodAbstract:A mutation in actVI-ORF1, which controls C-3 reduction in actinorhodin biosynthesis by Streptomyces Coelicolor, was complemented by gra-ORF5 and -ORF6 from the granaticin biosynthetic gene cluster of Streptomyces violaceoruber Tu22. It is hypothesized that, while gra-ORF5 alone is a ketoreductase for C-9, gra-ORF6 gives the enzyme regiospecificity also for C-3.
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proof that the actvi genetic region of Streptomyces Coelicolor a3 2 is involved in stereospecific pyran ring formation in the biosynthesis of actinorhodin
Bioorganic & Medicinal Chemistry Letters, 1999Co-Authors: Koji Ichinose, Chandres Surti, Takaaki Taguchi, Kevin I Bookermilburm, Yutaka Ebizuka, Richard G Stephenson, Francisco Malpartida, David A HopwoodAbstract:Pyran ring formation in the biosynthesis of actinorhodin in Streptomyces Coelicolor A3(2) was studied using the act cluster deficient strain, CH999, carrying pRM5-based plasmids harbouring combinations of the actVI genes. The strain, CH999/pIJ5660 (pRM5 + actVI-ORF1), produced a chiral intermediate, (S)-DNPA, suggesting that the actVI-ORF1 product is a reductase determining the C-3 stereochemical centre.