Lobophorins(LOBs)belong to a large family of spirotetronate antibiotics with antibacterial and antitumor activities.In this study,we demonstrated the function of LobP1,a P450 monooxygenase encoded in the LOB biosynthe...Lobophorins(LOBs)belong to a large family of spirotetronate antibiotics with antibacterial and antitumor activities.In this study,we demonstrated the function of LobP1,a P450 monooxygenase encoded in the LOB biosynthetic gene cluster,by in vivo deletion and in vitro biochemical assays.The disruption of lobP1 led to the isolation of three new LOBs derivatives(3-5)and three known ones(6-8)without the hydroxyl group at C-32.LobP1 was shown to have relatively broad substrate scope.Determining the kinetic parameters of LobP1 towards different substrates revealed that LobP1 preferred substrate with a nitrosugar.The new LOBs 3-5 displayed significant antibacterial activities against Bacillus subtilis and Micrococcus luteus with MIC values of 0.125 to 1μg·mL^(-1),and the major product LOB E(6)from the∆lobP1 mutant showed moderate cytotoxic activities against several cancer cell lines.展开更多
Tiacumicin B(also known as fidaxomicin or difimicin)is a marketed 18-membered macrolide antibiotic for the treatment of Clostridium difficile infections.Tiacumicin B is structurally characterized with two chlorine ato...Tiacumicin B(also known as fidaxomicin or difimicin)is a marketed 18-membered macrolide antibiotic for the treatment of Clostridium difficile infections.Tiacumicin B is structurally characterized with two chlorine atoms substituted on the aromatic ring,which is installed by the halogenase Tia M.During the study on halide compatibility of Tia M,a facile and nonenzymatic iodination method of didechlorotiacumicin B was discovered,requiring Na I,acid and air for iodination at room temperature.This method was also amenable to other 9 aromatic substrates with electron-rich sites for iodination.展开更多
基金supported in part by the National Natural Science Foundation of China(22193072 and 32100045)the Key Science and Technology Project of Hainan Province(ZDKJ202018)+4 种基金MOST(2018YFA0901903)K.C.WongEducationnFoundation(GJTD-2020-12)the Guangdong Provincial Special Fund for Marine Economic Development Project(GDNRC[2021]48)the Science and Technology Planning Project of Guangzhou(202102020471)Rising Star Foundation of the South China Sea Institute of Oceanology(NHXX2018SW0201)。
文摘Lobophorins(LOBs)belong to a large family of spirotetronate antibiotics with antibacterial and antitumor activities.In this study,we demonstrated the function of LobP1,a P450 monooxygenase encoded in the LOB biosynthetic gene cluster,by in vivo deletion and in vitro biochemical assays.The disruption of lobP1 led to the isolation of three new LOBs derivatives(3-5)and three known ones(6-8)without the hydroxyl group at C-32.LobP1 was shown to have relatively broad substrate scope.Determining the kinetic parameters of LobP1 towards different substrates revealed that LobP1 preferred substrate with a nitrosugar.The new LOBs 3-5 displayed significant antibacterial activities against Bacillus subtilis and Micrococcus luteus with MIC values of 0.125 to 1μg·mL^(-1),and the major product LOB E(6)from the∆lobP1 mutant showed moderate cytotoxic activities against several cancer cell lines.
基金the Key Science and Technology Project of Hainan Province(Key Science and Technology Project ZDKJ202018)the Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou,2019ZD0406)+2 种基金the Chinese Academy of Sciences(QYZDJ-SSW-DQC004)the National Natural Science Foundation of China(81872778,31630004,41911530078)the Ministry of Science and Technology of China(2018YFC1406705)。
文摘Tiacumicin B(also known as fidaxomicin or difimicin)is a marketed 18-membered macrolide antibiotic for the treatment of Clostridium difficile infections.Tiacumicin B is structurally characterized with two chlorine atoms substituted on the aromatic ring,which is installed by the halogenase Tia M.During the study on halide compatibility of Tia M,a facile and nonenzymatic iodination method of didechlorotiacumicin B was discovered,requiring Na I,acid and air for iodination at room temperature.This method was also amenable to other 9 aromatic substrates with electron-rich sites for iodination.
