22 results on '"Yu, Yi"'
Search Results
2. Hydrogen peroxide promotes potassium uptake by activating flavonoid biosynthesis pathway and ethylene signaling in grapevines.
- Author
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Wei, Tong-Lu, Guo, Da-Long, Pei, Mao-Song, Wang, Ze-Hang, Liu, Hai-Nan, and Yu, Yi-He
- Subjects
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FLAVONOIDS , *HYDROGEN peroxide , *BIOSYNTHESIS , *POTASSIUM , *CROPS , *VITICULTURE , *RESVERATROL , *JASMONATE - Abstract
• Hydrogen peroxide (H 2 O 2) treatment improves K+ uptake in grapes. • H 2 O 2 treatment activates flavonoid biosynthesis pathway. • H 2 O 2 changes ethylene signaling to promote K+ uptake by regulating K+ transporters. Potassium ion (K+) is an essential nutrient for plants. Grapes are an important industrial crop with an extremely high demand for potassium. However, potassium deficiency occurs frequently in viticulture and greatly restricts the grape industry. Developing a technique to improve potassium uptake efficiency is of vital importance for grapes. In this study, we found that hydrogen peroxide (H 2 O 2) treatment could improve K+ uptake in grapes. To determine the mechanisms underlying H 2 O 2 -induced K+ uptake, transcriptome sequencing (RNA-seq) was conducted and the differentially expressed genes were further analyzed. Gene Ontology (GO) enrichment indicated that ion transport-related pathways and genes changed after H 2 O 2 treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and weighted gene co-expression network analysis (WGCNA) showed that the flavonoid biosynthesis pathway was closely related to H 2 O 2 -induced K+ uptake, and H 2 O 2 treatment could activate the flavonoid biosynthesis pathway. Further analysis demonstrated that H 2 O 2 treatment could activate ethylene synthesis and the ethylene signaling pathway, which promoted K+ uptake by regulating K+ transporter genes. Overall, this study demonstrates a new technique, H 2 O 2 treatment, for enhancing potassium uptake efficiency in grapes and reveals the molecular mechanisms underlying H 2 O 2 -induced K+ uptake. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
3. Two Cryptic Self‐Resistance Mechanisms in Streptomyces tenebrarius Reveal Insights into the Biosynthesis of Apramycin.
- Author
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Zhang, Qian, Chi, Hao‐Tian, Wu, Linrui, Deng, Zixin, and Yu, Yi
- Subjects
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DEACETYLATION , *BIOSYNTHESIS , *STREPTOMYCES , *PHOSPHORYLATION , *ALKALINE phosphatase , *ACETYL group - Abstract
Apramycin is a clinically promising aminoglycoside antibiotic (AGA). To date, mechanisms underlying the biosynthesis and self‐resistance of apramycin remain largely unknown. Here we report that apramycin biosynthesis proceeds through unexpected phosphorylation, deacetylation, and dephosphorylation steps, in which a novel aminoglycoside phosphotransferase (AprU), a putative creatinine amidohydrolase (AprP), and an alkaline phosphatase (AprZ) are involved. Biochemical characterization revealed that AprU specifically phosphorylates 5‐OH of a pseudotrisaccharide intermediate, whose N‐7′ acetyl group is subsequently hydrolyzed by AprP. AprZ is located extracellularly where it removes the phosphate group from a pseudotetrasaccharide intermediate, leading to the maturation of apramycin. Intriguingly, 7′‐N‐acetylated and 5‐O‐phosphorylated apramycin that were accumulated in ΔaprU and ΔaprZ respectively exhibited significantly reduced antibacterial activities, implying Streptomyces tenebrarius employs C‐5 phosphorylation and N‐7′ acetylation as two strategies to avoid auto‐toxicity. Significantly, this study provides insight into the design of new generation AGAs to circumvent the emergence of drug‐resistant pathogens. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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4. Two Cryptic Self‐Resistance Mechanisms in Streptomyces tenebrarius Reveal Insights into the Biosynthesis of Apramycin.
- Author
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Zhang, Qian, Chi, Hao‐Tian, Wu, Linrui, Deng, Zixin, and Yu, Yi
- Subjects
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DEACETYLATION , *BIOSYNTHESIS , *STREPTOMYCES , *PHOSPHORYLATION , *ALKALINE phosphatase , *ACETYL group - Abstract
Apramycin is a clinically promising aminoglycoside antibiotic (AGA). To date, mechanisms underlying the biosynthesis and self‐resistance of apramycin remain largely unknown. Here we report that apramycin biosynthesis proceeds through unexpected phosphorylation, deacetylation, and dephosphorylation steps, in which a novel aminoglycoside phosphotransferase (AprU), a putative creatinine amidohydrolase (AprP), and an alkaline phosphatase (AprZ) are involved. Biochemical characterization revealed that AprU specifically phosphorylates 5‐OH of a pseudotrisaccharide intermediate, whose N‐7′ acetyl group is subsequently hydrolyzed by AprP. AprZ is located extracellularly where it removes the phosphate group from a pseudotetrasaccharide intermediate, leading to the maturation of apramycin. Intriguingly, 7′‐N‐acetylated and 5‐O‐phosphorylated apramycin that were accumulated in ΔaprU and ΔaprZ respectively exhibited significantly reduced antibacterial activities, implying Streptomyces tenebrarius employs C‐5 phosphorylation and N‐7′ acetylation as two strategies to avoid auto‐toxicity. Significantly, this study provides insight into the design of new generation AGAs to circumvent the emergence of drug‐resistant pathogens. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
5. The Biosynthesis of the Benzoxazole in Nataxazole Proceeds via an Unstable Ester and has Synthetic Utility.
- Author
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Song, Haigang, Rao, Cong, Deng, Zixin, Yu, Yi, and Naismith, James H.
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BENZOXAZOLE , *BENZOXAZOLES , *BIOSYNTHESIS , *PROCEEDS , *NATURAL products , *HETEROCYCLIC compounds , *ESTERS - Abstract
Heterocycles, a class of molecules that includes oxazoles, constitute one of the most common building blocks in current pharmaceuticals and are common in medicinally important natural products. The antitumor natural product nataxazole is a model for a large class of benzoxazole‐containing molecules that are made by a pathway that is not characterized. We report structural, biochemical, and chemical evidence that benzoxazole biosynthesis proceeds through an ester generated by an ATP‐dependent adenylating enzyme. The ester rearranges via a tetrahedral hemiorthoamide to yield an amide, which is a shunt product and not, as previously thought, an intermediate in the pathway. A second zinc‐dependent enzyme catalyzes the formation of hemiorthoamide from the ester but, by shuttling protons, the enzyme eliminates water, a reverse hydrolysis reaction, to yield the benzoxazole and avoids the amide. These insights have allowed us to harness the pathway to synthesize a series of novel halogenated benzoxazoles. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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6. The Biosynthesis of the Benzoxazole in Nataxazole Proceeds via an Unstable Ester and has Synthetic Utility.
- Author
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Song, Haigang, Rao, Cong, Deng, Zixin, Yu, Yi, and Naismith, James H.
- Subjects
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BENZOXAZOLES , *BENZOXAZOLE , *BIOSYNTHESIS , *PROCEEDS , *NATURAL products , *HETEROCYCLIC compounds , *ESTERS - Abstract
Heterocycles, a class of molecules that includes oxazoles, constitute one of the most common building blocks in current pharmaceuticals and are common in medicinally important natural products. The antitumor natural product nataxazole is a model for a large class of benzoxazole‐containing molecules that are made by a pathway that is not characterized. We report structural, biochemical, and chemical evidence that benzoxazole biosynthesis proceeds through an ester generated by an ATP‐dependent adenylating enzyme. The ester rearranges via a tetrahedral hemiorthoamide to yield an amide, which is a shunt product and not, as previously thought, an intermediate in the pathway. A second zinc‐dependent enzyme catalyzes the formation of hemiorthoamide from the ester but, by shuttling protons, the enzyme eliminates water, a reverse hydrolysis reaction, to yield the benzoxazole and avoids the amide. These insights have allowed us to harness the pathway to synthesize a series of novel halogenated benzoxazoles. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
7. The Catalytic Mechanism of the Class C Radical S-Adenosylmethionine Methyltransferase NosN.
- Author
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Li, Yongzhen, Ji, Xinjian, Mo, Tianlu, Qianzhu, Haocheng, Tu, Tao, Chen, Fener, Zhang, Qi, Ding, Wei, Zhao, Junfeng, Deng, Zixin, and Yu, Yi
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ADENOSYLMETHIONINE , *CATALYTIC activity , *METHYLATION , *ENZYME activation , *METHYLTRANSFERASES - Abstract
S-Adenosylmethionine (SAM) is one of the most common co-substrates in enzyme-catalyzed methylation reactions. Most SAM-dependent reactions proceed through an SN2 mechanism, whereas a subset of them involves radical intermediates for methylating non-nucleophilic substrates. Herein, we report the characterization and mechanistic investigation of NosN, a class C radical SAM methyltransferase involved in the biosynthesis of the thiopeptide antibiotic nosiheptide. We show that, in contrast to all known SAM-dependent methyltransferases, NosN does not produce S-adenosylhomocysteine (SAH) as a co-product. Instead, NosN converts SAM into 5′-methylthioadenosine as a direct methyl donor, employing a radical-based mechanism for methylation and releasing 5′-thioadenosine as a co-product. A series of biochemical and computational studies allowed us to propose a comprehensive mechanism for NosN catalysis, which represents a new paradigm for enzyme-catalyzed methylation reactions. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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8. The Catalytic Mechanism of the Class C Radical S-Adenosylmethionine Methyltransferase NosN.
- Author
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Ding, Wei, Li, Yongzhen, Zhao, Junfeng, Ji, Xinjian, Mo, Tianlu, Qianzhu, Haocheng, Tu, Tao, Deng, Zixin, Yu, Yi, Chen, Fener, and Zhang, Qi
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ADENOSYLMETHIONINE , *CHEMICAL radical synthesis , *METHYLTRANSFERASES , *BIOSYNTHESIS , *METHYLATION , *NATURAL products , *THIOPEPTIDES - Abstract
S-Adenosylmethionine (SAM) is one of the most common co-substrates in enzyme-catalyzed methylation reactions. Most SAM-dependent reactions proceed through an SN2 mechanism, whereas a subset of them involves radical intermediates for methylating non-nucleophilic substrates. Herein, we report the characterization and mechanistic investigation of NosN, a class C radical SAM methyltransferase involved in the biosynthesis of the thiopeptide antibiotic nosiheptide. We show that, in contrast to all known SAM-dependent methyltransferases, NosN does not produce S-adenosylhomocysteine (SAH) as a co-product. Instead, NosN converts SAM into 5′-methylthioadenosine as a direct methyl donor, employing a radical-based mechanism for methylation and releasing 5′-thioadenosine as a co-product. A series of biochemical and computational studies allowed us to propose a comprehensive mechanism for NosN catalysis, which represents a new paradigm for enzyme-catalyzed methylation reactions. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
9. Revisiting the transcriptome data of Centella asiatica identified an ester-forming triterpenoid: UDP-glucose 28-O-glucosyltransferase.
- Author
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Han, Xiaoyang, Zhao, Jingyi, Chang, Xuancheng, Li, Qiuyun, Deng, Zixin, and Yu, Yi
- Subjects
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CENTELLA asiatica , *TRANSCRIPTOMES , *URIDINE diphosphate , *SAPONINS , *TRITERPENOIDS , *CARBOXYL group , *NATURAL products - Abstract
Advances in sequencing technologies have produced a huge amount of transcriptome data, which facilitate the revelation of natural product biosynthetic pathways in plants. Asiaticoside and madecassoside are two famous triterpene saponins with unusual glucose-glucose-rhamnose chain at the C-28 position of the aglycone. To date, the complete glycosylation pathway underlying the assembly of the above sugar chain remains largely unknown. Here we successfully screened out 75 putative uridine diphosphate (UDP)-dependent glycosyltransferases (UGTs) by analyzing the latest transcriptome data of Centella asiatica. We further identified a UGT (CaUGT1) that could specifically transfer the glucose to the C-28 carboxyl group of asiatic acid and madecassic acid. Interestingly, the expression profile of CaUGT1 is highly correlated with UGT73AD1, a previously characterized UDP-glucose 28-O-glucosyltransferase, suggesting that the initial glycosylation step of asiatic acid and madecassic acid was synergistically catalyzed by these two UGTs. This study thus laid the foundation for a comprehensively understanding of the glycosylation network in the biosynthesis of asiaticoside and madecassoside. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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10. Biosynthesis of Neocarazostatin A Reveals the Sequential Carbazole Prenylation and Hydroxylation in the Tailoring Steps.
- Author
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Huang, Sheng, Elsayed, Somayah Sameer, Lv, Meinan, Tabudravu, Jioji, Rateb, Mostafa E., Gyampoh, Roland, Kyeremeh, Kwaku, Ebel, Rainer, Jaspars, Marcel, Deng, Zixin, Yu, Yi, and Deng, Hai
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ALKALOIDS , *BIOSYNTHESIS , *CARBAZOLE , *ORGANIC synthesis , *AROMATIC compounds - Abstract
Summary Neocarazostatin A (NZS) is a bacterial alkaloid with promising bioactivities against free radicals, featuring a tricyclic carbazole nucleus with a prenyl moiety at C-6 of the carbazole ring. Here, we report the discovery and characterization of the biosynthetic pathway of NZS through genome mining and gene inactivation. The in vitro assays characterized two enzymes: NzsA is a P450 hydroxylase and NzsG is a new phytoene-synthase-like prenyltransferase (PTase). This is the first reported native PTase that specifically acts on the carbazole nucleus. Finally, our in vitro reconstituted experiment demonstrated a coupled reaction catalyzed by NzsG and NzsA tailoring the NZS biosynthesis. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
11. Characterization of the Biosynthetic Gene Cluster for Benzoxazole Antibiotics A33853 Reveals Unusual Assembly Logic.
- Author
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Lv, Meinan, Zhao, Junfeng, Deng, Zixin, and Yu, Yi
- Subjects
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BIOSYNTHESIS , *BENZOXAZOLES , *ANTIBIOTICS assay , *CLUSTER analysis (Statistics) , *CLUSTERING of particles , *COENZYME A - Abstract
Summary A33853, which shows excellent bioactivity against Leishmania , is a benzoxazole-family compound formed from two moieties of 3-hydroxyanthranilic acid and one 3-hydroxypicolinic acid. In this study, we have identified the gene cluster responsible for the biosynthesis of A33853 in Streptomyces sp. NRRL12068 through genome mining and heterologous expression. Bioinformatics analysis and functional characterization of the orf s contained in the gene cluster revealed that the biosynthesis of A33853 is directed by a group of unusual enzymes. In particular, BomK, annotated as a ketosynthase, was found to catalyze the amide bond formation between 3-hydroxypicolinic and 3-hydroxyanthranilic acid during the assembly of A33853. BomJ, a putative ATP-dependent coenzyme A ligase, and BomN, a putative amidohydrolase, were further proposed to be involved in the benzoxazole formation in A33853 according to gene deletion experiments. Finally, we have successfully utilized mutasynthesis to generate two analogs of A33853, which were reported previously to possess excellent anti-leishmanial activity. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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12. Discovery of a Single Monooxygenase that Catalyzes Carbamate Formation and Ring Contraction in the Biosynthesis of the Legonmycins.
- Author
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Huang, Sheng, Tabudravu, Jioji, Elsayed, Somayah S., Travert, Jeanne, Peace, Doe, Tong, Ming Him, Kyeremeh, Kwaku, Kelly, Sharon M., Trembleau, Laurent, Ebel, Rainer, Jaspars, Marcel, Yu, Yi, and Deng, Hai
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MONOOXYGENASES , *NATURAL products , *PYRROLIZIDINES , *XENOGRAFTS , *GENE silencing - Abstract
Pyrrolizidine alkaloids (PAs) are a group of natural products with important biological activities. The discovery and characterization of the multifunctional FAD-dependent enzyme LgnC is now described. The enzyme is shown to convert indolizidine intermediates into pyrrolizidines through an unusual ring expansion/contraction mechanism, and catalyze the biosynthesis of new bacterial PAs, the so-called legonmycins. By genome-driven analysis, heterologous expression, and gene inactivation, the legonmycins were also shown to originate from non-ribosomal peptide synthetases (NRPSs). The biosynthetic origin of bacterial PAs has thus been disclosed for the first time. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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13. Mining of the Pyrrolamide Antibiotics Analogs in Streptomyces netropsis Reveals the Amidohydrolase-Dependent “Iterative Strategy” Underlying the Pyrrole Polymerization.
- Author
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Hao, Chunlin, Huang, Sheng, Deng, Zixin, Zhao, Changming, and Yu, Yi
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STREPTOMYCES , *AMIDASES , *PYRROLES , *POLYMERIZATION , *ANTIBIOTICS , *BIOSYNTHESIS , *DRUG development - Abstract
In biosynthesis of natural products, potential intermediates or analogs of a particular compound in the crude extracts are commonly overlooked in routine assays due to their low concentration, limited structural information, or because of their insignificant bio-activities. This may lead into an incomplete and even an incorrect biosynthetic pathway for the target molecule. Here we applied multiple compound mining approaches, including genome scanning and precursor ion scan-directed mass spectrometry, to identify potential pyrrolamide compounds in the fermentation culture of Streptomyces netropsis. Several novel congocidine and distamycin analogs were thus detected and characterized. A more reasonable route for the biosynthesis of pyrrolamides was proposed based on the structures of these newly discovered compounds, as well as the functional characterization of several key biosynthetic genes of pyrrolamides. Collectively, our results implied an unusual “iterative strategy” underlying the pyrrole polymerization in the biosynthesis of pyrrolamide antibiotics. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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14. Disruption of a methyltransferase gene in actinomycin G gene cluster in Streptomyces iakyrus increases the production of phenazinomycin.
- Author
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Qin, Zhiwei, Wang, Xiaoling, Rateb, Mostafa Ezzat, Ass'ad, Lina Adnan, Jaspars, Marcel, Deng, Zixin, Yu, Yi, and Deng, Hai
- Subjects
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METHYLTRANSFERASES , *ACTINOMYCES , *PHENAZINE , *DOXORUBICIN , *LEUKEMIA , *STREPTOMYCES , *GENE expression - Abstract
Phenazinomycin is a hybrid natural product consisting of two chemical entities, a phenazine and a cyclic terpenoid. Phenazinomycin exhibits potent activity against murine tumors and adriamycin-resistant P388 leukemia cells. Streptomyces iakyrus DSM 41873 is known to produce five actinomycin G2- G6. In the previous study, we identified the gene cluster directing the biosynthesis of actinomycin G2-G4. Inactivation of acm G5′ gene in the actinomycin G gene cluster in S. iakyrus completely abolished the production of actinomycin G. Metabolic profiling, chemical isolation, and structural elucidation of the resulting mutant SIAΔ acm G5′ showed a previously unnoticed metabolite phenazinomycin in S. iakyrus. In silico analysis identified a hybrid biosynthetic gene cluster in the genome of S. iakyrus that could be responsible for the biosynthesis of phenazinomycin. It is proposed that the perturbation of actinomycin G to enhance the phenazinomycin production in the mutant may result from the lifted competition of chorismate, the common precursor of the biosynthetic pathways of these two structurally unrelated natural products. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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15. A facile whole-cell biocatalytic approach to regioselective synthesis of monoacylated 1-β-d-arabinofuranosylcytosine: Influence of organic solvents
- Author
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Li, Xiao-feng, Lu, Zhi-hong, Zhao, Guang-lei, Wu, Hui, and Yu, Yi-gang
- Subjects
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PSEUDOMONAS fluorescens , *ORGANIC solvents , *BACTERIAL cells , *BIOSYNTHESIS , *ACYLATION , *CYTARABINE , *ENZYMES , *TEMPERATURE effect - Abstract
Abstract: The lyophilized Pseudomonas fluorescens cell was an efficient alternative catalyst to enzymes for highly regioselective acylation of a polar nucleoside, 1-β-d-arabinofuranosylcytosine (ara-C). The cells showed an evident solvent dependence in the reaction. Among the tested solvents except for acetonitrile–pyridine, catalytic activity of the cells clearly increased with increasing the polarity of the organic solvents used. Among all the tested solvents both pure and binary, the best results were observed in isopropyl ether–pyridine system, in which the catalyst also showed good thermal and operational stabilities. For the biocataylsis in isopropyl ether–pyridine, the optimal isopropyl ether concentration, water content, acyl donor/ara-C ratio, biocatalyst dosage and reaction temperature were 30% (v/v), 4%, 45, 50mg/mL and 30°C, respectively, under which the initial rate, yield and 5′-regioselectivity were 2.93mM/h, 77.1% and 97.3%, respectively. The bacterial cells exhibited comparable 5′-regioselectivity to the expensive immobilized enzyme, which could also have environmental and cost advantages. [Copyright &y& Elsevier]
- Published
- 2012
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16. A novel biocatalytic approach to acetylation of 1-β- d-arabinofuranosylcytosine by Aspergillus oryzae whole cell in organic solvents.
- Author
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Li, Xiao-Feng, Zhu, Zhen, Zhao, Guang-Lei, Yu, Yi-Gang, Lai, Fu-Rao, and Wu, Hui
- Subjects
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ACETYLATION , *KOJI , *NUCLEAR magnetic resonance , *GLUCOSE , *MALTOSE , *OLEIC acid , *BIOSYNTHESIS , *NUCLEOSIDES - Abstract
Biocatalytic acylation of 1-β- d-arabinofuranosylcytosine (ara-C) was developed using whole cell of Aspergillus oryzae as a novel catalyst. C nuclear magnetic resonance (NMR) analysis indicated that the whole-cell biocatalyst had more specific activity toward the 3′-hydroxyl group than 5′-hydroxyl group among the available hydroxyl groups in sugar moiety of ara-C. Except for glucose and maltose, 11 carbon sources supplemented to basal media, including Spans, Tweens, olive oil and oleic acid, exhibited notable enhancement effects on both the cell growth and the acylation reactions. It was suggested that the carbon sources containing controlled-release oleic acid were the important substrates for the production of fungal cell-bound lipase with specific activity, partially due to a gradual induction effect of their released oleic acid on the cell-bound lipase production. Despite the low initial reaction rate and substrate conversion, the addition of 2.0 g/l Span 80 resulted in a higher 3′-regioselectivity of the cells than 81%. By using Tween 85 at its optimum concentration of 5.0 g/l, however, the highest initial rates (3.2 mmol/l h) and substrate conversion (76%) of the whole-cell catalyzed acylation of ara-C can be achieved. It was also found that the 3′-regioselectivity of the cells showed observable increase by extending the culture time. And the activity of cell-bound lipase drastically increased in the early stage of cell growth and then declined in the late culture stage, whatever the culture media used. Our results thus indicated that A. oryzae whole cell was a promising green tool for biosynthesis of nucleoside esters with potential bioactivities. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
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17. Identification and heterologous expression of the biosynthetic gene cluster for holomycin produced by Streptomyces clavuligerus
- Author
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Huang, Sheng, Zhao, Yudong, Qin, Zhiwei, Wang, Xiaoling, Onega, Mayca, Chen, Li, He, Jing, Yu, Yi, and Deng, Hai
- Subjects
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GENE expression , *BIOSYNTHESIS , *LIGASES , *BIOINFORMATICS , *STREPTOMYCES , *RING formation (Chemistry) - Abstract
Abstract: Holomycin is a dithiolopyrrolone antibiotic natural product produced by Streptomyces clavuligerus, ATCC 27064. This paper reports on the identification of a gene cluster from S. clavuligerus that directs holomycin biosynthesis. Heterologous expression of the cluster in S. albus then induced the production of holomycin. Bioinformatics analysis of the gene cluster revealed that holomycin was assembled by a single multidomain non-ribosomal peptide synthetase (NRPS) consisting of heterocyclization, adenylation, and thiolation domains (Cy-A-T), a free-standing condensation domain, two thioesterases, five tailoring enzymes involved in oxidative reactions and two regulatory and transcriptional genes. Knock out of the gene, HomI, completely abolished the production of holomycin, which is consistent with its role as a key biosynthetic gene and is likely involved in the formation of the disulfide bond generating the final precursor, holothin. [Copyright &y& Elsevier]
- Published
- 2011
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18. Characterization of the Azinomycin B Biosynthetic Gene Cluster Revealing a Different Iterative Type I Polyketide Synthase for Naphthoate Biosynthesis
- Author
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Zhao, Qunfei, He, Qingli, Ding, Wei, Tang, Mancheng, Kang, Qianjin, Yu, Yi, Deng, Wei, Zhang, Qi, Fang, Jie, Tang, Gongli, and Liu, Wen
- Subjects
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BIOSYNTHESIS , *PEPTIDES , *LIGASES , *BIOCHEMISTRY - Abstract
Summary: Azinomycin B is a complex natural product containing densely assembled functionalities with potent antitumor activity. Cloning and sequence analysis of the azi gene cluster revealed an iterative type I polyketide synthase (PKS) gene, five nonribosomal peptide synthetases (NRPSs) genes and numerous genes encoding the biosynthesis of unusual building blocks and tailoring steps for azinomycin B production. Characterization of AziB as a 5-methyl-naphthoic acid (NPA) synthase showed a distinct selective reduction pattern in aromatic polyketide biosynthesis governed by bacterial iterative type I PKSs. Heterologous expression established the PKS-post modification route from 5-methyl-NPA to reach the first building block 3-methoxy-5-methyl-NPA. This proposed azinomycin B biosynthetic pathway sets the stage to investigate the enzymatic mechanisms for building structurally unique and pharmaceutically important groups, including the unprecedented azabicyclic ring system and highly active epoxide moiety. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
19. Functional Analysis of the Validamycin Biosynthetic Gene Cluster and Engineered Production of Validoxylamine A
- Author
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Bai, Linquan, Li, Lei, Xu, Hui, Minagawa, Kazuyuki, Yu, Yi, Zhang, Yirong, Zhou, Xiufen, Floss, Heinz G., Mahmud, Taifo, and Deng, Zixin
- Subjects
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FUNCTIONAL analysis , *BIOSYNTHESIS , *GENETIC transformation , *NUCLEOTIDE sequence - Abstract
Summary: A 45 kb DNA sequencing analysis from Streptomyces hygroscopicus 5008 involved in validamycin A (VAL-A) biosynthesis revealed 16 structural genes, 2 regulatory genes, 5 genes related transport, transposition/integration or tellurium resistance; another 4 genes had no obvious identity. The VAL-A biosynthetic pathway was proposed, with assignment of the required genetic functions confined to the sequenced region. A cluster of eight reassembled genes was found to support VAL-A synthesis in a heterologous host, S. lividans 1326. In vivo inactivation of the putative glycosyltransferase gene (valG) abolished the final attachment of glucose for VAL production and resulted in accumulation of the VAL-A precursor, validoxylamine, while the normal production of VAL-A could be restored by complementation with valG. The role of valG in the glycosylation of validoxylamine to VAL-A was demonstrated in vitro by enzymatic assay. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
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20. Inside Cover: The Catalytic Mechanism of the Class C Radical S-Adenosylmethionine Methyltransferase NosN (Angew. Chem. Int. Ed. 14/2017).
- Author
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Li, Yongzhen, Ji, Xinjian, Mo, Tianlu, Qianzhu, Haocheng, Tu, Tao, Chen, Fener, Zhang, Qi, Ding, Wei, Zhao, Junfeng, Deng, Zixin, and Yu, Yi
- Subjects
- *
CATALYTIC activity , *CHEMICAL reactions , *METHYLATION - Published
- 2017
- Full Text
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21. Back Cover: Discovery of a Single Monooxygenase that Catalyzes Carbamate Formation and Ring Contraction in the Biosynthesis of the Legonmycins (Angew. Chem. Int. Ed. 43/2015).
- Author
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Huang, Sheng, Tabudravu, Jioji, Elsayed, Somayah S., Travert, Jeanne, Peace, Doe, Tong, Ming Him, Kyeremeh, Kwaku, Kelly, Sharon M., Trembleau, Laurent, Ebel, Rainer, Jaspars, Marcel, Yu, Yi, and Deng, Hai
- Subjects
- *
INDOLIZIDINES , *PYRROLIZIDINES , *CARBAMATES - Abstract
The multifunctional Baeyer–Villiger enzyme LgnC catalyzes the transformation of indolizidines into pyrrolizidines by carbamate formation, hydrolysis, decarboxylation‐driven ring contraction, and hydroxylation. In their Communication on page 12697 ff., H. Deng, Y. Yu et al. show that these are the crucial steps for the biosynthesis of the legonmycins, new bacterial pyrrolizidine alkaloids named after their association with Legon, Ghana. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
22. Structure-based Mechanistic Insights into Terminal Amide Synthase in Nosiheptide-Represented Thiopeptides Biosynthesis.
- Author
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Liu, Shanshan, Guo, Heng, Zhang, Tianlong, Han, Li, Yao, Pengfei, Zhang, Yan, Rong, Naiyan, Yu, Yi, Lan, Wenxian, Wang, Chunxi, Ding, Jianping, Wang, Renxiao, Liu, Wen, and Cao, Chunyang
- Subjects
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AMIDE synthesis , *THIOPEPTIDES , *BIOSYNTHESIS , *C-terminal residues , *CATALYTIC activity - Abstract
Nosiheptide is a parent compound of thiopeptide family that exhibit potent activities against various bacterial pathogens. Its C-terminal amide formation is catalyzed by NosA, which is an unusual strategy for maturating certain thiopeptides by processing their precursor peptides featuring a serine extension. We here report the crystal structure of truncated NosA1-111 variant, revealing three key elements, including basic lysine 49 (K49), acidic glutamic acid 101 (E101) and flexible C-terminal loop NosA112-151, are crucial to the catalytic terminal amide formation in nosiheptide biosynthesis. The side-chain of residue K49 and the C-terminal loop fasten the substrate through hydrogen bonds and hydrophobic interactions. The side-chain of residue E101 enhances nucleophilic attack of H2O to the methyl imine intermediate, leading to Cα-N bond cleavage and nosiheptide maturation. The sequence alignment of NosA and its homologs NocA, PbtH, TpdK and BerI, and the enzymatic assay suggest that the mechanistic studies on NosA present an intriguing paradigm about how NosA family members function during thiopeptide biosynthesis. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
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Catalog
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