Characterization of the P450 Monooxygenase LobP1 as C-32 Hydroxylase in Lobophorin Biosynthesis  

作　　者：Bin Tan Qingbo Zhang Ji Xiao Chengshan Yuan Yuchan Chen Siqiang Chen Weimin Zhang Yiguang Zhu Changsheng Zhang 

机构地区：[1]Key Laboratory of Tropical Marine Bioresources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, Guangdong, 510301 China [2]University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing, 100049 China [3]Sanya Institute of Ocean Eco-Environmental Engineering, Yazhou Scientific Bay, Sanya, Hainan, 572000 China [4]State Key Laboratory of Applied Microbiology Southern China, Guangzhong Provincial Key Laboratory of Microbial Culture Collection and Application, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510070 China

出　　处：《Chinese Journal of Chemistry》2023年第12期1478-1484,共7页中国化学（英文版）

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);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)。

摘　　要：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.

关 键 词：Lobophorins BIOSYNTHESIS Post modifications P450 monooxygenase HYDROXYLATION Enzymes Biological activity Structure elucidation 

分 类 号：O62[理学—有机化学]