The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Hung-wen Liu - One of the best experts on this subject based on the ideXlab platform.
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Identification of the Formycin A Biosynthetic Gene Cluster from Streptomyces kaniharaensis Illustrates the Interplay between Biological Pyrazolopyrimidine Formation and de Novo Purine Biosynthesis.
Journal of the American Chemical Society, 2019Co-Authors: Shao-an Wang, Jia Zeng, Yujie Geng, Daan Ren, Yasushi Ogasawara, Seema Irani, Yan Zhang, Hung-wen LiuAbstract:Formycin A is a potent purine Nucleoside Antibiotic with a C-glycosidic linkage between the ribosyl moiety and the pyrazolopyrimidine base. Herein, a cosmid is identified from the Streptomyces kaniharaensis genome library that contains the for gene cluster responsible for the biosynthesis of formycin. Subsequent gene deletion experiments and in vitro characterization of the forBCH gene products established their catalytic functions in formycin biosynthesis. Results also demonstrated that PurH from de novo purine biosynthesis plays a key role in pyrazolopyrimidine formation during biosynthesis of formycin A. The participation of PurH in both pathways represents a good example of how primary and secondary metabolism are interlinked.
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Identification of the Formycin A Biosynthetic Gene Cluster from Streptomyces kaniharaensis Illustrates the Interplay between Biological Pyrazolopyrimidine Formation and de Novo Purine Biosynthesis
2019Co-Authors: Shao-an Wang, Jia Zeng, Yujie Geng, Daan Ren, Yasushi Ogasawara, Seema Irani, Yan Zhang, Hung-wen LiuAbstract:Formycin A is a potent purine Nucleoside Antibiotic with a C-glycosidic linkage between the ribosyl moiety and the pyrazolopyrimidine base. Herein, a cosmid is identified from the Streptomyces kaniharaensis genome library that contains the for gene cluster responsible for the biosynthesis of formycin. Subsequent gene deletion experiments and in vitro characterization of the forBCH gene products established their catalytic functions in formycin biosynthesis. Results also demonstrated that PurH from de novo purine biosynthesis plays a key role in pyrazolopyrimidine formation during biosynthesis of formycin A. The participation of PurH in both pathways represents a good example of how primary and secondary metabolism are interlinked
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identification and interrogation of the herbicidin biosynthetic gene cluster first insight into the biosynthesis of a rare undecose Nucleoside Antibiotic
Journal of the American Chemical Society, 2017Co-Authors: Gengmin Lin, Anthony J Romo, Priscilla H Liem, Zhang Chen, Hung-wen LiuAbstract:Herbicidins are adenosine-based Nucleoside Antibiotics with an unusual tricyclic undecose core decorated with a (5-hydroxy)tiglyl moiety. Feeding studies are herein reported demonstrating that the tricyclic core is derived from d-glucose and d-ribose, whereas the tiglyl moiety is derived from an intermediate of l-isoleucine catabolism. Identification of the gene cluster for herbicidin A biosynthesis in Streptomyces sp. L-9-10 as well as its verification by heterologous expression in a nonproducing host are described, and the results of in vitro characterization of a carboxyl methyltransferase encoded in the cluster, Her8, are presented. Based on these observations, a biosynthetic pathway is proposed for herbicidins.
James H Naismith - One of the best experts on this subject based on the ideXlab platform.
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pmp diketopiperazine adducts form at the active site of a plp dependent enzyme involved in formycin biosynthesis
Chemical Communications, 2019Co-Authors: Sisi Gao, H Liu, Valerie De Crecylagard, Wen Zhu, Nigel G J Richards, James H NaismithAbstract:ForI is a PLP-dependent enzyme from the biosynthetic pathway of the C-Nucleoside Antibiotic formycin. Cycloserine is thought to inhibit PLP-dependent enzymes by irreversibly forming a PMP–isoxazole. We now report that ForI forms novel PMP–diketopiperazine derivatives following incubation with both D and L cycloserine. This unexpected result suggests chemical diversity in the chemistry of cycloserine inhibition.
Daniel Wiegmann - One of the best experts on this subject based on the ideXlab platform.
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pyridoxal 5 phosphate dependent alkyl transfer in Nucleoside Antibiotic biosynthesis
Nature Chemical Biology, 2020Co-Authors: Zheng Cui, Jonathan Overbay, Xiachang Wang, Xiaodong Liu, Yinan Zhang, Minakshi Bhardwaj, Anke Lemke, Daniel WiegmannAbstract:Several Nucleoside Antibiotics are structurally characterized by a 5″-amino-5″-deoxyribose (ADR) appended via a glycosidic bond to a high-carbon sugar Nucleoside (5′S,6′S)-5′-C-glycyluridine (GlyU). GlyU is further modified with an N-alkylamine linker, the biosynthetic origin of which has yet to be established. By using a combination of feeding experiments with isotopically labeled precursors and characterization of recombinant proteins from multiple pathways, the biosynthetic mechanism for N-alkylamine installation for ADR–GlyU-containing Nucleoside Antibiotics has been uncovered. The data reveal S-adenosyl-l-methionine (AdoMet) as the direct precursor of the N-alkylamine, but, unlike conventional AdoMet- or decarboxylated AdoMet-dependent alkyltransferases, the reaction is catalyzed by a pyridoxal-5′-phosphate-dependent aminobutyryltransferase (ABTase) using a stepwise γ-replacement mechanism that couples γ-elimination of AdoMet with aza-γ-addition onto the disaccharide alkyl acceptor. In addition to using a conceptually different strategy for AdoMet-dependent alkylation, the newly discovered ABTases require a phosphorylated disaccharide alkyl acceptor, revealing a cryptic intermediate in the biosynthetic pathway. Rather than a typical S-adenosylmethionine-dependent alkyltransferase, the installation of the N-alkylamine linker in several Nucleoside Antibiotics is catalyzed via γ-replacement by a pyridoxal-5′-phosphate-dependent aminobutyryltransferase.
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pyridoxal 5 phosphate dependent alkyl transfer in Nucleoside Antibiotic biosynthesis
Nature Chemical Biology, 2020Co-Authors: Zheng Cui, Jonathan Overbay, Xiachang Wang, Xiaodong Liu, Yinan Zhang, Minakshi Bhardwaj, Anke Lemke, Daniel WiegmannAbstract:Several Nucleoside Antibiotics are structurally characterized by a 5″-amino-5″-deoxyribose (ADR) appended via a glycosidic bond to a high-carbon sugar Nucleoside (5'S,6'S)-5'-C-glycyluridine (GlyU). GlyU is further modified with an N-alkylamine linker, the biosynthetic origin of which has yet to be established. By using a combination of feeding experiments with isotopically labeled precursors and characterization of recombinant proteins from multiple pathways, the biosynthetic mechanism for N-alkylamine installation for ADR-GlyU-containing Nucleoside Antibiotics has been uncovered. The data reveal S-adenosyl-L-methionine (AdoMet) as the direct precursor of the N-alkylamine, but, unlike conventional AdoMet- or decarboxylated AdoMet-dependent alkyltransferases, the reaction is catalyzed by a pyridoxal-5'-phosphate-dependent aminobutyryltransferase (ABTase) using a stepwise γ-replacement mechanism that couples γ-elimination of AdoMet with aza-γ-addition onto the disaccharide alkyl acceptor. In addition to using a conceptually different strategy for AdoMet-dependent alkylation, the newly discovered ABTases require a phosphorylated disaccharide alkyl acceptor, revealing a cryptic intermediate in the biosynthetic pathway.
Yinan Zhang - One of the best experts on this subject based on the ideXlab platform.
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pyridoxal 5 phosphate dependent alkyl transfer in Nucleoside Antibiotic biosynthesis
Nature Chemical Biology, 2020Co-Authors: Zheng Cui, Jonathan Overbay, Xiachang Wang, Xiaodong Liu, Yinan Zhang, Minakshi Bhardwaj, Anke Lemke, Daniel WiegmannAbstract:Several Nucleoside Antibiotics are structurally characterized by a 5″-amino-5″-deoxyribose (ADR) appended via a glycosidic bond to a high-carbon sugar Nucleoside (5′S,6′S)-5′-C-glycyluridine (GlyU). GlyU is further modified with an N-alkylamine linker, the biosynthetic origin of which has yet to be established. By using a combination of feeding experiments with isotopically labeled precursors and characterization of recombinant proteins from multiple pathways, the biosynthetic mechanism for N-alkylamine installation for ADR–GlyU-containing Nucleoside Antibiotics has been uncovered. The data reveal S-adenosyl-l-methionine (AdoMet) as the direct precursor of the N-alkylamine, but, unlike conventional AdoMet- or decarboxylated AdoMet-dependent alkyltransferases, the reaction is catalyzed by a pyridoxal-5′-phosphate-dependent aminobutyryltransferase (ABTase) using a stepwise γ-replacement mechanism that couples γ-elimination of AdoMet with aza-γ-addition onto the disaccharide alkyl acceptor. In addition to using a conceptually different strategy for AdoMet-dependent alkylation, the newly discovered ABTases require a phosphorylated disaccharide alkyl acceptor, revealing a cryptic intermediate in the biosynthetic pathway. Rather than a typical S-adenosylmethionine-dependent alkyltransferase, the installation of the N-alkylamine linker in several Nucleoside Antibiotics is catalyzed via γ-replacement by a pyridoxal-5′-phosphate-dependent aminobutyryltransferase.
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pyridoxal 5 phosphate dependent alkyl transfer in Nucleoside Antibiotic biosynthesis
Nature Chemical Biology, 2020Co-Authors: Zheng Cui, Jonathan Overbay, Xiachang Wang, Xiaodong Liu, Yinan Zhang, Minakshi Bhardwaj, Anke Lemke, Daniel WiegmannAbstract:Several Nucleoside Antibiotics are structurally characterized by a 5″-amino-5″-deoxyribose (ADR) appended via a glycosidic bond to a high-carbon sugar Nucleoside (5'S,6'S)-5'-C-glycyluridine (GlyU). GlyU is further modified with an N-alkylamine linker, the biosynthetic origin of which has yet to be established. By using a combination of feeding experiments with isotopically labeled precursors and characterization of recombinant proteins from multiple pathways, the biosynthetic mechanism for N-alkylamine installation for ADR-GlyU-containing Nucleoside Antibiotics has been uncovered. The data reveal S-adenosyl-L-methionine (AdoMet) as the direct precursor of the N-alkylamine, but, unlike conventional AdoMet- or decarboxylated AdoMet-dependent alkyltransferases, the reaction is catalyzed by a pyridoxal-5'-phosphate-dependent aminobutyryltransferase (ABTase) using a stepwise γ-replacement mechanism that couples γ-elimination of AdoMet with aza-γ-addition onto the disaccharide alkyl acceptor. In addition to using a conceptually different strategy for AdoMet-dependent alkylation, the newly discovered ABTases require a phosphorylated disaccharide alkyl acceptor, revealing a cryptic intermediate in the biosynthetic pathway.
Xiachang Wang - One of the best experts on this subject based on the ideXlab platform.
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pyridoxal 5 phosphate dependent alkyl transfer in Nucleoside Antibiotic biosynthesis
Nature Chemical Biology, 2020Co-Authors: Zheng Cui, Jonathan Overbay, Xiachang Wang, Xiaodong Liu, Yinan Zhang, Minakshi Bhardwaj, Anke Lemke, Daniel WiegmannAbstract:Several Nucleoside Antibiotics are structurally characterized by a 5″-amino-5″-deoxyribose (ADR) appended via a glycosidic bond to a high-carbon sugar Nucleoside (5′S,6′S)-5′-C-glycyluridine (GlyU). GlyU is further modified with an N-alkylamine linker, the biosynthetic origin of which has yet to be established. By using a combination of feeding experiments with isotopically labeled precursors and characterization of recombinant proteins from multiple pathways, the biosynthetic mechanism for N-alkylamine installation for ADR–GlyU-containing Nucleoside Antibiotics has been uncovered. The data reveal S-adenosyl-l-methionine (AdoMet) as the direct precursor of the N-alkylamine, but, unlike conventional AdoMet- or decarboxylated AdoMet-dependent alkyltransferases, the reaction is catalyzed by a pyridoxal-5′-phosphate-dependent aminobutyryltransferase (ABTase) using a stepwise γ-replacement mechanism that couples γ-elimination of AdoMet with aza-γ-addition onto the disaccharide alkyl acceptor. In addition to using a conceptually different strategy for AdoMet-dependent alkylation, the newly discovered ABTases require a phosphorylated disaccharide alkyl acceptor, revealing a cryptic intermediate in the biosynthetic pathway. Rather than a typical S-adenosylmethionine-dependent alkyltransferase, the installation of the N-alkylamine linker in several Nucleoside Antibiotics is catalyzed via γ-replacement by a pyridoxal-5′-phosphate-dependent aminobutyryltransferase.
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pyridoxal 5 phosphate dependent alkyl transfer in Nucleoside Antibiotic biosynthesis
Nature Chemical Biology, 2020Co-Authors: Zheng Cui, Jonathan Overbay, Xiachang Wang, Xiaodong Liu, Yinan Zhang, Minakshi Bhardwaj, Anke Lemke, Daniel WiegmannAbstract:Several Nucleoside Antibiotics are structurally characterized by a 5″-amino-5″-deoxyribose (ADR) appended via a glycosidic bond to a high-carbon sugar Nucleoside (5'S,6'S)-5'-C-glycyluridine (GlyU). GlyU is further modified with an N-alkylamine linker, the biosynthetic origin of which has yet to be established. By using a combination of feeding experiments with isotopically labeled precursors and characterization of recombinant proteins from multiple pathways, the biosynthetic mechanism for N-alkylamine installation for ADR-GlyU-containing Nucleoside Antibiotics has been uncovered. The data reveal S-adenosyl-L-methionine (AdoMet) as the direct precursor of the N-alkylamine, but, unlike conventional AdoMet- or decarboxylated AdoMet-dependent alkyltransferases, the reaction is catalyzed by a pyridoxal-5'-phosphate-dependent aminobutyryltransferase (ABTase) using a stepwise γ-replacement mechanism that couples γ-elimination of AdoMet with aza-γ-addition onto the disaccharide alkyl acceptor. In addition to using a conceptually different strategy for AdoMet-dependent alkylation, the newly discovered ABTases require a phosphorylated disaccharide alkyl acceptor, revealing a cryptic intermediate in the biosynthetic pathway.
