Article
Chemistry, Physical
Qingwei Tian, Jingjing Deng, Jingting Wu, Zhangli Hu, Jianhua Ju, Liyan Wang
Summary: In this study, two monooxygenases, JuiN and JuiO, were found to catalyze hydroxylation and epoxidation reactions following C-C axis formation, leading to the natural product julichrome Q(6-6). The crystal structure of JuiN-FAD-Q(6-6) and mutagenesis experiments revealed the substrate recognition mechanisms for iterative hydroxylations along the C-C axis. Additionally, the unstable intermediate julichrome Q(8-8) was successfully captured, and an alternative enzyme SgJuiO was investigated for the same complex sequence of epoxidations.
Article
Chemistry, Multidisciplinary
Xinjie Shi, Liming Huang, Kaihui Song, Guiyun Zhao, Yu Liu, Longxian Lv, Yi-Ling Du
Summary: This study elucidates the key enzymes and catalytic mechanisms involved in the biosynthesis of luzopeptin A, with a cytochrome P450 enzyme identified as multitasking in several consecutive oxidation reactions, and a membrane-bound acyltransferase potentially mediating extracellular modifications. The findings provide mechanistic insights into P450-mediated carbon-nitrogen bond desaturation and expand the catalytic versatility of P450 family enzymes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Plant Sciences
Andrew Muchlinski, Meirong Jia, Kira Tiedge, Jason S. Fell, Kyle A. Pelot, Lisl Chew, Danielle Davisson, Yuxuan Chen, Justin Siegel, John T. Lovell, Philipp Zerbe
Summary: This study reports the discovery of five cytochrome P450 monooxygenases in switchgrass, forming previously unknown furanoditerpenoids. Combinatorial pathway reconstruction showed that these enzymes catalyze furan ring addition directly. Transcriptional co-expression patterns and the presence of specific diterpenoids in roots support the occurrence of P450-derived furanoditerpenoids in planta.
Article
Biochemistry & Molecular Biology
Aiko Teshima, Hisashi Kondo, Yu Tanaka, Yosi Nindita, Yuya Misaki, Yuji Konaka, Yasuhiro Itakura, Tsugumi Tonokawa, Haruyasu Kinashi, Kenji Arakawa
Summary: The study investigates the lankamycin biosynthetic pathway, focusing on two cytochrome P450 monooxygenases LkmK and LkmF. By constructing double mutants, it was confirmed that LkmK has a relaxed substrate specificity for 15-deoxy lankamycin derivatives, while LkmF has a strict substrate specificity in lankamycin biosynthesis, particularly recognizing the C-3 l-arcanosyl moiety.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yanhui Lu, Qi Bai, Qiang Li, Xusong Zheng, Junce Tian, Jiawen Guo, Hongxing Xu, Zhongxian Lu
Summary: The study identified and characterized two cytochrome P450 monooxygenase genes, CsCYP6SN3 and CsCYP306A1, associated with the lethal effect of vetiver against C. suppressalis larvae. Inhibition of these genes significantly reduced pupation rate and pupa weight in the pests.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Chemistry, Physical
Chun-Chi Chen, Meng Dai, Lilan Zhang, Jing Zhao, Wei Zeng, Min Shi, Jian-Wen Huang, Weidong Liu, Rey-Ting Guo, Aitao Li
Summary: We investigated the mechanism of the P450tol enzyme from Rhodococcus coprophilus TC-2, which can hydroxylate toluene at the benzylic site. We solved the crystal structures of P450tol and its complex with the substrate, revealing how P450tol restricts the binding position of toluene and enables precise hydroxylation at the benzylic site. Additionally, we found that P450tol can also hydroxylate larger substrates and synthesized a self-sufficient chimeric enzyme with improved activity and stability. These findings highlight the potential of P450tol in biotechnological and pharmaceutical applications.
Article
Biotechnology & Applied Microbiology
Dina Kacar, Librada M. Canedo, Pilar Rodriguez, Carmen Schleissner, Fernando de la Calle, Jose Luis Garcia, Beatriz Galan
Summary: Pederin-family polyketides, known for their extreme cytotoxic activity, are produced by various microorganisms. Research on the modification enzymes in the Lab gene cluster has led to the production of different tailored analogs of Labrenzin, contributing to the understanding of Pederin-family polyketides biosynthesis and providing tools for modifying and overproducing these anticancer drugs.
MICROBIAL BIOTECHNOLOGY
(2023)
Article
Microbiology
Qiumei Zhou, Jiuxiang Wang, Hui Jiang, Gaofei Wang, Yulong Wang
Summary: The study investigated the gene expression of Sanghuangporus vaninii at different developmental stages, revealing significant differences in the expression of P450 enzymes between mycelium and fruiting bodies. It was found that more genes involved in the biosynthesis of bioactive compounds were expressed at higher levels in mycelium under liquid medium culture, indicating that liquid fermentation is more suitable for producing bioactive compounds in Sanghuangporus vaninii.
ARCHIVES OF MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Narayanan Srividya, Iris Lange, Jana K. Richter, Matthias Wuest, B. Markus Lange
Summary: In this study, the enantioselectivity of multiple enzymes involved in monoterpenoid biosynthesis in peppermint and Japanese catnip was investigated. The experimental results showed that these enzymes exhibited different enantioselectivity towards intermediates of the pathway, and molecular modeling studies supported the experimental data. This study lays the groundwork for further structure-function studies on the origin of enantioselectivity in closely related species of the Lamiaceae.
Article
Biochemistry & Molecular Biology
Zhenyu Zhao, Dongfeng Yang, Juan Guo, Xiuyu Liu, Qishuang Li, Ping Su, Jian Wang, Ying Ma, Luqi Huang
Summary: This study cloned and studied 15 CYP76AH genes from 10 Salvia species from the perspectives of evolution and catalytic efficiency. Three CYP76AH genes with significantly improved catalytic efficiency compared to SmCYP76AH3 were identified, providing efficient catalytic elements for the synthetic biological production of tanshinones. A structure-function relationship study revealed several conserved residues that might be related to the function of CYP76AHs and provided a new mutation direction for the study of the directed evolution of plant P450.
Article
Chemistry, Multidisciplinary
Bin Tan, Qingbo Zhang, Ji Xiao, Chengshan Yuan, Yuchan Chen, Siqiang Chen, Weimin Zhang, Yiguang Zhu, Changsheng Zhang
Summary: In this study, the function of LobP1, a P450 monooxygenase encoded in the LOB biosynthetic gene cluster, was investigated through in vivo deletion and in vitro biochemical assays. LobP1 was shown to have a broad substrate scope, with a preference for substrates with a nitrosugar. The new LOBs derivatives exhibited significant antibacterial and cytotoxic activities against various bacteria and cancer cell lines.
CHINESE JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Organic
Jiadong Sun, Gengxiang Zhao, Robert D. OConnor, Jack R. Davison, Carole A. Bewley
Summary: Six novel pyranonaphthoquinones, named vertirhodins A-F, were discovered from a soil-derived Streptomyces sp. B15-008. Their chemical structures and absolute configurations were determined using nuclear magnetic resonance and comparison of experimental and theoretical electronic circular dichroism spectra. A plausible biosynthetic gene cluster for these compounds was identified through whole genome sequencing, providing insights into their unique structural features.
Article
Chemistry, Physical
Yaqin Peng, Chenghua Gao, Zili Zhang, Shijie Wu, Jing Zhao, Aitao Li
Summary: This study presents a chemoenzymatic strategy for the synthesis of steroid drugs and successfully achieves regio- and stereoselective modifications with high yields. It demonstrates great potential for industrial applications.
Article
Biochemistry & Molecular Biology
Jiawei Liu, Hongmin Hu, Huimin Shen, Qingyin Tian, Wenjie Ding, Xiulian Yang, Lianggui Wang, Yuanzheng Yue
Summary: This study identified a total of 276 P450 genes belonging to 40 families in Osmanthus fragrans, suggesting their potential roles in fragrance synthesis. The research provides valuable insights into the functions of P450 genes and serves as a guide for further studies on promoting fragrance biosynthesis in ornamental plants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Ren-Jie Li, Kaiyuan Tian, Xirui Li, Anand Raghavendra Gaikaiwari, Zhi Li
Summary: In this study, a group of P450BM3 mutants were developed as unique catalysts for regioselective hydroxylation reactions of aromatic compounds. The mutants showed high regioselectivity and conversion, leading to the production of valuable m-alkylbenzene-1,4-diols. Protein engineering and site-directed mutagenesis were used to reshape the substrate binding pocket and access channel of the P450BM3 monooxygenase. Molecular docking and simulation provided insights into the enhanced regioselectivity and activity of the mutants. The mutants were successfully applied in preparative biohydroxylation reactions for the synthesis of m-alkylbenzene-1,4-diols.
Review
Chemistry, Medicinal
Ge Yan, Yunfu Wang, Jincao Chen, Wenzhong Zheng, Changzhen Liu, Shi Chen, Lianrong Wang, Jie Luo, Zhiqiang Li
MEDICINAL RESEARCH REVIEWS
(2020)
Article
Microbiology
Xiaolin Xiong, Geng Wu, Yue Wei, Liqiong Liu, Yubing Zhang, Rui Su, Xianyue Jiang, Mengxue Li, Haiyan Gao, Xihao Tian, Yizhou Zhang, Li Hu, Si Chen, You Tang, Susu Jiang, Ruolin Huang, Zhiqiang Li, Yunfu Wang, Zixin Deng, Jiawei Wang, Peter C. Dedon, Shi Chen, Lianrong Wang
NATURE MICROBIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Bo Cao, Xiaolin Wu, Jieliang Zhou, Hang Wu, Lili Liu, Qinghua Zhang, Michael S. DeMott, Chen Gu, Lianrong Wang, Delin You, Peter C. Dedon
NUCLEIC ACIDS RESEARCH
(2020)
Article
Multidisciplinary Sciences
Xiaolin Wu, Bo Cao, Patricia Aquino, Tsu-Pei Chiu, Chao Chen, Susu Jiang, Zixin Deng, Shi Chen, Remo Rohs, Lianrong Wang, James E. Galagan, Peter C. Dedon
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Cell Biology
Cheng Zhang, Pengqing Nie, Chunliu Zhou, Yue Hu, Suling Duan, Meijia Gu, Dongxu Jiang, Yunfu Wang, Zixin Deng, Jincao Chen, Shi Chen, Lianrong Wang
Summary: In this study, mild and sustained hydrogen peroxide stimulation induced Parkin-dependent mitophagy while downregulating mitophagy-associated proteins OPTN, NDP52, and MFN2. The expression of the miR-106b-93-25 cluster was promoted by H2O2, leading to the inhibition of translation of mitophagy-associated proteins, thereby controlling excessive mitophagy and cell death. This research provides insight into a novel mechanism of mitophagy control through miRNA-mediated regulation.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Yue Wei, Qinqin Huang, Xihao Tian, Mingmin Zhang, Junkai He, Xingxiang Chen, Chao Chen, Zixin Deng, Zhiqiang Li, Shi Chen, Lianrong Wang
Summary: DNA phosphorothioate (PT) modifications, governed by specific proteins, exhibit a highly unusual distribution across individual DNA molecules. Single-molecule studies have shown that the PT profiles vary significantly among different molecules, providing new insights into the relationship between PT modifications and restriction components.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Infectious Diseases
Ze-Min Li, Xiao Xiao, Chuan-Min Zhou, Jian-Xiao Liu, Xiao-Lan Gu, Li-Zhu Fang, Bin-Yan Liu, Lian-Rong Wang, Xue-Jie Yu, Hui-Ju Han
Summary: The study found a new species of pathogenic Borrelia in bats in Hubei, China, suggesting potential public health risks associated with bats carrying this bacterium.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Microbiology
Wei He, Haiyan Gao, Dan Wu, Susu Jiang, Wanqiu Huang, Chao Chen, Zixin Deng, Lei Xiong, Geng Wu, Lianrong Wang
Summary: DndABCDE proteins catalyze DNA phosphorothioate (PT) modification by replacing the nonbridging oxygen with sulfur. DndA acts as a cysteine desulfurase in the pathway, mobilizing sulfur from l-cysteine with the help of DndC. While the functions of multiple enzymes in the PT system have been elucidated, the exact role of DndE remains unclear. The crystal structure of DndE from Natronorubrum bangense JCM10635 reveals its monomeric conformation and ability to introduce nicks to DNA, providing insights into its role in PT modification and sulfur incorporation mechanism.
Article
Microbiology
You Tang, Yue Hong, Li Liu, Xuan Du, Yaqi Ren, Susu Jiang, Wanjing Liu, Chen Chao, Zixin Deng, Lianrong Wang, Shi Chen
Summary: Since the discovery of DNA phosphorothioate (PT) modification systems in Streptomyces lividans in the 1980s, research on PT systems has yielded important findings. However, the functions of PT systems, particularly in genetic regulation, are largely unknown. This study reveals that the PT system in Salmonella enterica serovar Cerro 87 is involved in the transcriptional regulation of the torCAD operon, shedding light on a new function of PT systems.
Article
Chemistry, Multidisciplinary
Meijia Gu, Susu Jiang, Xiaoyu Xu, Ming-Yu Wu, Chao Chen, Yuncong Yuan, Qingrong Chen, Yidan Sun, Luojia Chen, Chao Shen, Peng Guo, Shujie Liu, Engui Zhao, Shi Chen, Sijie Chen
Summary: A highly efficient photodynamic dental therapy strategy is reported, using a photosensitizer with aggregation-induced emission characteristics, which can eradicate tooth biofilm and whiten teeth in a short time with minimal damage to the teeth.
Article
Multidisciplinary Sciences
Xuan Zou, Xiaohong Xiao, Ziran Mo, Yashi Ge, Xing Jiang, Ruolin Huang, Mengxue Li, Zixin Deng, Shi Chen, Lianrong Wang, Sang Yup Lee
Summary: In this study, E. coli host strains with broad antiphase activities were constructed by integrating the Ssp defense system into the genome and introducing mutations in key components essential for phage infection cycles. These engineered E. coli strains showed strong resistance against various phages without affecting cell growth and maintained the production capabilities of recombinant proteins even under high levels of phage challenge.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Congrui Xu, Jing Rao, Yuqing Xie, Jiajun Lu, Zhiqiang Li, Changjiang Dong, Lianrong Wang, Jinghong Jiang, Chao Chen, Shi Chen
Summary: This study demonstrated the effect of DNA PT modification-based restriction-modification (R-M) systems on horizontal gene transfer (HGT) of antimicrobial resistance (AMR) genes in pathogenic bacteria. The presence of PT R-M effectively reduced the distribution of HGT-derived AMR genes in the genome and suppressed HGT frequency. There is no coevolution between PT R-M clusters and bacterial core genes.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Physical
Dan Wu, Yaqian Tang, Siwei Chen, Yue He, Xiaofei Chang, Wenzhong Zheng, Zixin Deng, Zhiqiang Li, Lianrong Wang, Geng Wu, Shi Chen
Summary: This study reveals that the proteins DndF, DndG, and DndH form a DndFGH complex that exhibits DNA nicking and translocation activities. The complex shows a preferential affinity for phosphorothioate DNA, which inhibits its activity. These findings expand our understanding of the defense mechanisms for protecting self-DNA involving epigenetic markers.
Article
Microbiology
Susu Jiang, Ke Chen, Yingying Wang, Yueying Zhang, Yaru Tang, Wanqiu Huang, Xiaolin Xiong, Shi Chen, Chao Chen, Lianrong Wang
Summary: Recently, we have decoded the mechanism of Dnd-related R-M systems against genetic parasites. The presence of exogenous DNA lacking PT triggers conformational changes in the DndF, DndG, and DndH macromolecular machine, enabling it to bind, translocate, and nick DNA, effectively neutralizing foreign DNA. Our study reveals that the host can benefit from Dnd-related R-M systems in a broad range of antiphage activities, independent of DNA methylation. Additionally, the convergence of Dnd- and Ssp-related R-M systems enhances the host's antiphage ability through the additive suppression of phage replication.
