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Chunjiang Wang - One of the best experts on this subject based on the ideXlab platform.
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exo selective construction of spiro Butyrolactone pyrrolidine via 1 3 dipolar cycloaddition of azomethine ylides with α methylene γ Butyrolactone catalyzed by cu i dtbm biphep
Chemical Communications, 2013Co-Authors: Tanglin Liu, Liang Wei, Xiang Zhou, Haiyan Tao, Chunjiang WangAbstract:An expedient access to optically active spiro-[Butyrolactone-pyrrolidine] was successfully developed via an unprecedented Cu(I)-catalyzed exo-selective 1,3-DC of azomethine ylides with α-methylene-γ-Butyrolactone, which exhibited high diastereoselectivity (>98 : 2), excellent enantioselectivity (96–>99% ee) and a broad substrate scope under mild conditions.
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catalytic asymmetric construction of spiro γ butyrolactam γ Butyrolactone moieties through sequential reactions of cyclic imino esters with morita baylis hillman bromides
Chemistry: A European Journal, 2012Co-Authors: Huailong Teng, Chunjiang Wang, He HuangAbstract:Spiro(γ-butyrolactam-γ-Butyrolactone): a route to enantioenriched spiro(γ-butyrolactam-γ-Butyrolactone) compounds, a valuable motif for drug discovery, was developed by use of a highly efficient copper(I)/TF-BiphamPhos-catalyzed tandem Michael addition-elimination of homoserine lactone derived cyclic imino esters with Morita-Baylis-Hillman (MBH) bromides, followed by treatment with para-toluenesulfonic acid.
Jianjiang Zhong - One of the best experts on this subject based on the ideXlab platform.
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exogenous 1 4 Butyrolactone stimulates a factor like cascade and validamycin biosynthesis in streptomyces hygroscopicus 5008
Biotechnology and Bioengineering, 2013Co-Authors: Gaoyi Tan, Linquan Bai, Jianjiang ZhongAbstract:γ-Butyrolactones (GBLs), such as A-factor, are one type of signaling molecules produced by Streptomyces species and have been reported to regulate secondary metabolism. However, they are usually produced in very small amount, which has hindered their structural elucidation and application for antibiotic overproduction. In this work, 1,4-Butyrolactone (1,4-BL), as an easily accessible and cheap analogue of GBLs, was applied to the fermentation of validamycin A (VAL-A), an important antifungal antibiotic produced by Streptomyces hygroscopicus 5008. The addition of 1,4-BL enhanced VAL-A production by 30% in both shaking flasks and bioreactors. The transcriptional levels of the adpA homologue (adpA-H) and VAL-A biosynthetic genes were significantly increased. Among the three A-factor receptor homologous genes identified in the genome of S. hygroscopicus 5008, shbR3 was proved to be responsible for the inducing activity of 1,4-BL by gene disruption and circular dichroism analysis, and ShbR3 could bind to the promoter region of adpA-H as indicated by EMSA analysis. Furthermore, the mutation of adpA-H abolished the transcription of VAL-A biosynthetic genes and VAL-A productivity. In EMSA analysis, AdpA-H could directly bind to the promoter regions of VAL-A gene cluster. Moreover, addition of the 1,4-BL also improved the VAL-A production in a high-yielding strain TL01. The results showed that 1,4-BL could stimulate A-factor-like cascade and subsequently enhance VAL-A production in S. hygroscopicus 5008.
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exogenous 1 4 Butyrolactone stimulates a factor like cascade and validamycin biosynthesis in streptomyces hygroscopicus 5008
Biotechnology and Bioengineering, 2013Co-Authors: Gaoyi Tan, Linquan Bai, Jianjiang ZhongAbstract:γ-Butyrolactones (GBLs), such as A-factor, are one type of signaling molecules produced by Streptomyces species and have been reported to regulate secondary metabolism. However, they are usually produced in very small amount, which has hindered their structural elucidation and application for antibiotic overproduction. In this work, 1,4-Butyrolactone (1,4-BL), as an easily accessible and cheap analogue of GBLs, was applied to the fermentation of validamycin A (VAL-A), an important antifungal antibiotic produced by Streptomyces hygroscopicus 5008. The addition of 1,4-BL enhanced VAL-A production by 30% in both shaking flasks and bioreactors. The transcriptional levels of the adpA homologue (adpA–H) and VAL-A biosynthetic genes were significantly increased. Among the three A-factor receptor homologous genes identified in the genome of S. hygroscopicus 5008, shbR3 was proved to be responsible for the inducing activity of 1,4-BL by gene disruption and circular dichroism analysis, and ShbR3 could bind to the promoter region of adpA–H as indicated by EMSA analysis. Furthermore, the mutation of adpA–H abolished the transcription of VAL-A biosynthetic genes and VAL-A productivity. In EMSA analysis, AdpA–H could directly bind to the promoter regions of VAL-A gene cluster. Moreover, addition of the 1,4-BL also improved the VAL-A production in a high-yielding strain TL01. The results showed that 1,4-BL could stimulate A-factor-like cascade and subsequently enhance VAL-A production in S. hygroscopicus 5008. Biotechnol. Bioeng. 2013;110: 2984–2993. © 2013 Wiley Periodicals, Inc.
Eriko Takano - One of the best experts on this subject based on the ideXlab platform.
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deletion of the signalling molecule synthase scba has pleiotropic effects on secondary metabolite biosynthesis morphological differentiation and primary metabolism in streptomyces coelicolor a3 2
Microbial Biotechnology, 2011Co-Authors: Davide Dalia, Daniela Eggle, Kay Nieselt, Rainer Breitling, Eriko TakanoAbstract:Streptomycetes have high biotechnological relevance as producers of diverse metabolites widely used in medical and agricultural applications. The biosynthesis of these metabolites is controlled by signalling molecules, γ‐Butyrolactones, that act as bacterial hormones. In Streptomyces coelicolor, a group of signalling molecules called SCBs (S. coelicolorbutanolides) regulates production of the pigmented antibiotics coelicolor polyketide (CPK), actinorhodin and undecylprodigiosin. The γ‐Butyrolactone synthase ScbA is responsible for the biosynthesis of SCBs. Here we show the results of a genome‐wide transcriptome analysis of a scbA deletion mutant prior to and during the transition to antibiotic production. We report a strong perturbation in the expression of three pigmented antibiotic clusters in the mutant throughout the growth curve, thus providing a molecular explanation for the antibiotic phenotype observed previously. Our study also revealed, for the first time, that the secondary metabolite cluster responsible for synthesis of the siderophore desferrioxamine is under the control of SCB signalling. Moreover, expression of the genes encoding enzymes for primary metabolism pathways, which supply antibiotic precursors and genes for morphological differentiation, was found shifted earlier in time in the mutant. In conclusion, our time series analysis demonstrates new details of the regulatory effects of the γ‐Butyrolactone system in Streptomyces.
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a bistable gene switch for antibiotic biosynthesis the Butyrolactone regulon in streptomyces coelicolor
PLOS ONE, 2008Co-Authors: Sarika Mehra, Salim Charaniya, Eriko TakanoAbstract:Many microorganisms, including bacteria of the class Streptomycetes, produce various secondary metabolites including antibiotics to gain a competitive advantage in their natural habitat. The production of these compounds is highly coordinated in a population to expedite accumulation to an effective concentration. Furthermore, as antibiotics are often toxic even to their producers, a coordinated production allows microbes to first arm themselves with a defense mechanism to resist their own antibiotics before production commences. One possible mechanism of coordination among individuals is through the production of signaling molecules. The γ-Butyrolactone system in Streptomyces coelicolor is a model of such a signaling system for secondary metabolite production. The accumulation of these signaling molecules triggers antibiotic production in the population. A pair of repressor-amplifier proteins encoded by scbA and scbR mediates the production and action of one particular γ-Butyrolactone, SCB1. Based on the proposed interactions of scbA and scbR, a mathematical model was constructed and used to explore the ability of this system to act as a robust genetic switch. Stability analysis shows that the Butyrolactone system exhibits bistability and, in response to a threshold SCB1 concentration, can switch from an OFF state to an ON state corresponding to the activation of genes in the cryptic type I polyketide synthase gene cluster, which are responsible for production of the hypothetical polyketide. The switching time is inversely related to the inducer concentration above the threshold, such that short pulses of low inducer concentration cannot switch on the system, suggesting its possible role in noise filtering. In contrast, secondary metabolite production can be triggered rapidly in a population of cells producing the Butyrolactone signal due to the presence of an amplification loop in the system. S. coelicolor was perturbed experimentally by varying concentrations of SCB1, and the model simulations match the experimental data well. Deciphering the complexity of this Butyrolactone switch will provide valuable insights into how robust and efficient systems can be designed using “simple” two-protein networks.
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a complex role for the γ Butyrolactone scb1 in regulating antibiotic production in streptomyces coelicolor a3 2
Molecular Microbiology, 2008Co-Authors: Eriko Takano, Takuya Nihira, Rekha Chakraburtty, Yashuhiro Yamada, Mervyn J BibbAbstract:Summary Many streptomycetes produce extracellular g-Butyrolactones. In several cases, these have been shown to act as signals for the onset of antibiotic production. Synthesis of these molecules appears to require a member of the AfsA family of proteins (AfsA is required for A-factor synthesis of the g-Butyrolactone A-factor and consequently for streptomycin production in Streptomyces griseus ). An afsA homologue, scbA, was identified in Streptomyces coelicolor A3(2) and was found to lie adjacent to a divergently transcribed gene, scbR, which encodes a g-Butyrolactone binding protein. Gel retardation assays and DNase I footprinting studies revealed DNA binding sites for ScbR at 2 4t o2 33 nt with respect to the scbA transcriptional start site, and at 2 42 to 2 68 nt with respect to the scbR transcriptional start site. Addition of the g-Butyrolactone SCB1 of S. coelicolor resulted in loss of the DNA-binding ability of ScbR. A scbA mutant produced no gButyrolactones, yet overproduced two antibiotics, actinorhodin (Act) and undecylprodigiosin (Red), whereas a deletion mutant of scbR also failed to make g-Butyrolactones and showed delayed Red production. These phenotypes differ markedly from those expected by analogy with the S. griseus A-factor system. Furthermore, transcription of scbR increased, and that of scbA was abolished, in an scbR mutant, indicating that ScbR represses its own expression while activating that of scbA. In the scbA mutant, expression of both genes was greatly reduced. Addition of SCB1 to the scbA mutant induced transcription of scbR, but did not restore scbA expression, indicating that the deficiency in scbA transcription in the scbA mutant is not solely due to the inability to produce SCB1, and that ScbA is a positive autoregulator in addition to being required for g-Butyrolactone production. Overall, these results indicate a complex mechanism for g-Butyrolactonemediated regulation of antibiotic biosynthesis in S. coelicolor.
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scba from streptomyces coelicolor a3 2 has homology to fatty acid synthases and is able to synthesize Butyrolactones
Microbiology, 2007Co-Authors: Nai Hua Hsiao, Johannes Soding, Dirk Linke, Carinna Lange, Christian Hertweck, Wolfgang Wohlleben, Eriko TakanoAbstract:γ-Butyrolactones play an important role in the regulation of antibiotic production and differentiation in Streptomyces. However the biosynthetic pathway for these small molecules has not yet been determined, and in vitro synthesis has not been reported. The function of the AfsA family of proteins, originally proposed to catalyse γ-Butyrolactone synthesis, has been in debate. To clarify the function of the AfsA family, and to understand the synthesis of the γ-Butyrolactones, we performed in silico analysis of this protein family. AfsA proteins consist of two divergent domains, each of which has similarity to the fatty acid synthesis enzymes FabA and FabZ. The two predicted active sites in ScbA, which is the AfsA orthologue found in Streptomyces coelicolor, were mutated, and γ-Butyrolactone biosynthesis was abolished in all four constructed mutants, strongly suggesting that ScbA has enzymic activity.
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a bacterial hormone the scb1 directly controls the expression of a pathway specific regulatory gene in the cryptic type i polyketide biosynthetic gene cluster of streptomyces coelicolor
Molecular Microbiology, 2005Co-Authors: Eriko Takano, Takuya Nihira, Wolfgang Wohlleben, Mervyn J Bibb, Hiroshi Kinoshita, Vassilis Mersinias, Giselda Bucca, Graham Hotchkiss, Colin P Smith, Keith F ChaterAbstract:Gamma-Butyrolactone signalling molecules are produced by many Streptomyces species, and several have been shown to regulate antibiotic production. In Streptomyces coelicolor A3(2) at least one γ-Butyrolactone (SCB1) has been shown to stimulate antibiotic production, and genes encoding proteins that are involved in its synthesis (scbA) and binding (scbR) have been characterized. Expression of these genes is autoregulated by a complex mechanism involving the γ-Butyrolactone. In this study, additional genes influenced by ScbR were identified by DNA microarray analysis, and included a cryptic cluster of genes for a hypothetical type I polyketide. Further analysis of this gene cluster revealed that the pathway-specific regulatory gene, kasO, is a direct target for regulation by ScbR. Gel retardation and DNase I footprinting analyses identified two potential binding sites for ScbR, one at -3 to -35 nt and the other at -222 to -244 nt upstream of the kasO transcriptional start site. Addition of SCB1 eliminated the DNA binding activity of ScbR at both sites. The expression of kasO was growth phase regulated in the parent (maximal during transition phase), undetectable in a scbA null mutant, and constitutively expressed in a scbR null mutant. Addition of SCB1 to the scbA mutant restored the expression of kasO, indicating that ScbR represses kasO until transition phase, when presumably SCB1 accumulates in sufficient quantity to relieve kasO repression. Expression of the cryptic antibiotic gene cluster was undetectable in a kasO deletion mutant. This is the first report with comprehensive in vivo and in vitro data to show that a γ-Butyrolactone-binding protein directly regulates a secondary metabolite pathway-specific regulatory gene in Streptomyces.
Gaoyi Tan - One of the best experts on this subject based on the ideXlab platform.
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exogenous 1 4 Butyrolactone stimulates a factor like cascade and validamycin biosynthesis in streptomyces hygroscopicus 5008
Biotechnology and Bioengineering, 2013Co-Authors: Gaoyi Tan, Linquan Bai, Jianjiang ZhongAbstract:γ-Butyrolactones (GBLs), such as A-factor, are one type of signaling molecules produced by Streptomyces species and have been reported to regulate secondary metabolism. However, they are usually produced in very small amount, which has hindered their structural elucidation and application for antibiotic overproduction. In this work, 1,4-Butyrolactone (1,4-BL), as an easily accessible and cheap analogue of GBLs, was applied to the fermentation of validamycin A (VAL-A), an important antifungal antibiotic produced by Streptomyces hygroscopicus 5008. The addition of 1,4-BL enhanced VAL-A production by 30% in both shaking flasks and bioreactors. The transcriptional levels of the adpA homologue (adpA-H) and VAL-A biosynthetic genes were significantly increased. Among the three A-factor receptor homologous genes identified in the genome of S. hygroscopicus 5008, shbR3 was proved to be responsible for the inducing activity of 1,4-BL by gene disruption and circular dichroism analysis, and ShbR3 could bind to the promoter region of adpA-H as indicated by EMSA analysis. Furthermore, the mutation of adpA-H abolished the transcription of VAL-A biosynthetic genes and VAL-A productivity. In EMSA analysis, AdpA-H could directly bind to the promoter regions of VAL-A gene cluster. Moreover, addition of the 1,4-BL also improved the VAL-A production in a high-yielding strain TL01. The results showed that 1,4-BL could stimulate A-factor-like cascade and subsequently enhance VAL-A production in S. hygroscopicus 5008.
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exogenous 1 4 Butyrolactone stimulates a factor like cascade and validamycin biosynthesis in streptomyces hygroscopicus 5008
Biotechnology and Bioengineering, 2013Co-Authors: Gaoyi Tan, Linquan Bai, Jianjiang ZhongAbstract:γ-Butyrolactones (GBLs), such as A-factor, are one type of signaling molecules produced by Streptomyces species and have been reported to regulate secondary metabolism. However, they are usually produced in very small amount, which has hindered their structural elucidation and application for antibiotic overproduction. In this work, 1,4-Butyrolactone (1,4-BL), as an easily accessible and cheap analogue of GBLs, was applied to the fermentation of validamycin A (VAL-A), an important antifungal antibiotic produced by Streptomyces hygroscopicus 5008. The addition of 1,4-BL enhanced VAL-A production by 30% in both shaking flasks and bioreactors. The transcriptional levels of the adpA homologue (adpA–H) and VAL-A biosynthetic genes were significantly increased. Among the three A-factor receptor homologous genes identified in the genome of S. hygroscopicus 5008, shbR3 was proved to be responsible for the inducing activity of 1,4-BL by gene disruption and circular dichroism analysis, and ShbR3 could bind to the promoter region of adpA–H as indicated by EMSA analysis. Furthermore, the mutation of adpA–H abolished the transcription of VAL-A biosynthetic genes and VAL-A productivity. In EMSA analysis, AdpA–H could directly bind to the promoter regions of VAL-A gene cluster. Moreover, addition of the 1,4-BL also improved the VAL-A production in a high-yielding strain TL01. The results showed that 1,4-BL could stimulate A-factor-like cascade and subsequently enhance VAL-A production in S. hygroscopicus 5008. Biotechnol. Bioeng. 2013;110: 2984–2993. © 2013 Wiley Periodicals, Inc.
Linquan Bai - One of the best experts on this subject based on the ideXlab platform.
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exogenous 1 4 Butyrolactone stimulates a factor like cascade and validamycin biosynthesis in streptomyces hygroscopicus 5008
Biotechnology and Bioengineering, 2013Co-Authors: Gaoyi Tan, Linquan Bai, Jianjiang ZhongAbstract:γ-Butyrolactones (GBLs), such as A-factor, are one type of signaling molecules produced by Streptomyces species and have been reported to regulate secondary metabolism. However, they are usually produced in very small amount, which has hindered their structural elucidation and application for antibiotic overproduction. In this work, 1,4-Butyrolactone (1,4-BL), as an easily accessible and cheap analogue of GBLs, was applied to the fermentation of validamycin A (VAL-A), an important antifungal antibiotic produced by Streptomyces hygroscopicus 5008. The addition of 1,4-BL enhanced VAL-A production by 30% in both shaking flasks and bioreactors. The transcriptional levels of the adpA homologue (adpA-H) and VAL-A biosynthetic genes were significantly increased. Among the three A-factor receptor homologous genes identified in the genome of S. hygroscopicus 5008, shbR3 was proved to be responsible for the inducing activity of 1,4-BL by gene disruption and circular dichroism analysis, and ShbR3 could bind to the promoter region of adpA-H as indicated by EMSA analysis. Furthermore, the mutation of adpA-H abolished the transcription of VAL-A biosynthetic genes and VAL-A productivity. In EMSA analysis, AdpA-H could directly bind to the promoter regions of VAL-A gene cluster. Moreover, addition of the 1,4-BL also improved the VAL-A production in a high-yielding strain TL01. The results showed that 1,4-BL could stimulate A-factor-like cascade and subsequently enhance VAL-A production in S. hygroscopicus 5008.
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exogenous 1 4 Butyrolactone stimulates a factor like cascade and validamycin biosynthesis in streptomyces hygroscopicus 5008
Biotechnology and Bioengineering, 2013Co-Authors: Gaoyi Tan, Linquan Bai, Jianjiang ZhongAbstract:γ-Butyrolactones (GBLs), such as A-factor, are one type of signaling molecules produced by Streptomyces species and have been reported to regulate secondary metabolism. However, they are usually produced in very small amount, which has hindered their structural elucidation and application for antibiotic overproduction. In this work, 1,4-Butyrolactone (1,4-BL), as an easily accessible and cheap analogue of GBLs, was applied to the fermentation of validamycin A (VAL-A), an important antifungal antibiotic produced by Streptomyces hygroscopicus 5008. The addition of 1,4-BL enhanced VAL-A production by 30% in both shaking flasks and bioreactors. The transcriptional levels of the adpA homologue (adpA–H) and VAL-A biosynthetic genes were significantly increased. Among the three A-factor receptor homologous genes identified in the genome of S. hygroscopicus 5008, shbR3 was proved to be responsible for the inducing activity of 1,4-BL by gene disruption and circular dichroism analysis, and ShbR3 could bind to the promoter region of adpA–H as indicated by EMSA analysis. Furthermore, the mutation of adpA–H abolished the transcription of VAL-A biosynthetic genes and VAL-A productivity. In EMSA analysis, AdpA–H could directly bind to the promoter regions of VAL-A gene cluster. Moreover, addition of the 1,4-BL also improved the VAL-A production in a high-yielding strain TL01. The results showed that 1,4-BL could stimulate A-factor-like cascade and subsequently enhance VAL-A production in S. hygroscopicus 5008. Biotechnol. Bioeng. 2013;110: 2984–2993. © 2013 Wiley Periodicals, Inc.
