{"title":"在体内和体外重组 N-异戊烯基化吩嗪的生物合成,发现多种吩嗪修饰酶。","authors":"Teruhito Kato, Dan Xia, Taro Ozaki, Tomoyo Nakao, Ping Zhao, Makoto Nishiyama, Taro Shiraishi, Tomohisa Kuzuyama","doi":"10.1002/cbic.202400723","DOIUrl":null,"url":null,"abstract":"<p>Phenazine natural products play various roles such as signal molecules, antibiotics, or electron carriers in their producer strains. Among these products, phenazinomycin and lavanducyanin, which are produced by <i>Streptomyces</i> species, are characterized by an <i>N</i>-alkyl modification. Herein, we established the biosynthetic pathways for these two phenazine natural products. Gene-disruption experiments and <i>in vitro</i> reconstitution of the phenazine-tailoring pathway revealed the late steps of the biosynthetic pathway of the phenazines. The class II terpene cyclase homolog Pzm1 catalyzes the cyclization reaction of farnesyl diphosphate to form monocyclic farnesyl diphosphate. Additionally, the prenyltransferase homolog PzmP functions as the <i>N</i>-prenyltransferase of 5,10-dihydrophenazine-1-carboxylic acid. The flavin monooxygenase homolog PzmS catalyzes the oxidative decarboxylation of prenylated 5,10-dihydrophenazine-1-carboxylic acid to yield phenazinomycin. This study highlights unprecedented modification enzymes for phenazine natural products.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 2","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776366/pdf/","citationCount":"0","resultStr":"{\"title\":\"In vivo and in vitro Reconstitution of Biosynthesis of N-Prenylated Phenazines Revealing Diverse Phenazine-Modifying Enzymes\",\"authors\":\"Teruhito Kato, Dan Xia, Taro Ozaki, Tomoyo Nakao, Ping Zhao, Makoto Nishiyama, Taro Shiraishi, Tomohisa Kuzuyama\",\"doi\":\"10.1002/cbic.202400723\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Phenazine natural products play various roles such as signal molecules, antibiotics, or electron carriers in their producer strains. Among these products, phenazinomycin and lavanducyanin, which are produced by <i>Streptomyces</i> species, are characterized by an <i>N</i>-alkyl modification. Herein, we established the biosynthetic pathways for these two phenazine natural products. Gene-disruption experiments and <i>in vitro</i> reconstitution of the phenazine-tailoring pathway revealed the late steps of the biosynthetic pathway of the phenazines. The class II terpene cyclase homolog Pzm1 catalyzes the cyclization reaction of farnesyl diphosphate to form monocyclic farnesyl diphosphate. Additionally, the prenyltransferase homolog PzmP functions as the <i>N</i>-prenyltransferase of 5,10-dihydrophenazine-1-carboxylic acid. The flavin monooxygenase homolog PzmS catalyzes the oxidative decarboxylation of prenylated 5,10-dihydrophenazine-1-carboxylic acid to yield phenazinomycin. This study highlights unprecedented modification enzymes for phenazine natural products.</p>\",\"PeriodicalId\":140,\"journal\":{\"name\":\"ChemBioChem\",\"volume\":\"26 2\",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-10-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776366/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ChemBioChem\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cbic.202400723\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ChemBioChem","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cbic.202400723","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
In vivo and in vitro Reconstitution of Biosynthesis of N-Prenylated Phenazines Revealing Diverse Phenazine-Modifying Enzymes
Phenazine natural products play various roles such as signal molecules, antibiotics, or electron carriers in their producer strains. Among these products, phenazinomycin and lavanducyanin, which are produced by Streptomyces species, are characterized by an N-alkyl modification. Herein, we established the biosynthetic pathways for these two phenazine natural products. Gene-disruption experiments and in vitro reconstitution of the phenazine-tailoring pathway revealed the late steps of the biosynthetic pathway of the phenazines. The class II terpene cyclase homolog Pzm1 catalyzes the cyclization reaction of farnesyl diphosphate to form monocyclic farnesyl diphosphate. Additionally, the prenyltransferase homolog PzmP functions as the N-prenyltransferase of 5,10-dihydrophenazine-1-carboxylic acid. The flavin monooxygenase homolog PzmS catalyzes the oxidative decarboxylation of prenylated 5,10-dihydrophenazine-1-carboxylic acid to yield phenazinomycin. This study highlights unprecedented modification enzymes for phenazine natural products.
期刊介绍:
ChemBioChem (Impact Factor 2018: 2.641) publishes important breakthroughs across all areas at the interface of chemistry and biology, including the fields of chemical biology, bioorganic chemistry, bioinorganic chemistry, synthetic biology, biocatalysis, bionanotechnology, and biomaterials. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies, and supported by the Asian Chemical Editorial Society (ACES).