Review
Pharmacology & Pharmacy
Song Gao, Rongjin Sun, Rashim Singh, Sik Yu So, Clement T. Y. Chan, Tor Savidge, Ming Hu
Summary: This article reviews the role of gmGUS in host health, its impact on compound disposition, models used to study its activity, and discusses the prospects and challenges in developing drugs by targeting gmGUS.
DRUG DISCOVERY TODAY
(2022)
Article
Chemistry, Multidisciplinary
Cheng-Peng Sun, Xiang-Ge Tian, Lei Feng, Chao Wang, Jing-Xin Li, Xiao-Kui Huo, Wen-Yu Zhao, Jing Ning, Zhen-Long Yu, Sa Deng, Bao-Jing Zhang, Xia Lv, Jie Hou, Xiao-Chi Ma
Summary: The study found that ethanol extracts of black tea showed significant inhibitory activities against Escherichia coli beta-glucuronidase, with some polyphenols being identified as stronger inhibitors. This provides important information for the development of black tea and its constituents for treating drug-induced enteropathy.
ARABIAN JOURNAL OF CHEMISTRY
(2021)
Review
Cell Biology
Yue Sui, Jianming Wu, Jianping Chen
Summary: In recent years, there has been increasing attention on the role of gut microbial beta-glucuronidase in the pathogenesis of breast cancer due to its ability to reactivate estrogen. Although research in this area is still in its early stages, investigators have begun to explore the relationship between microbial beta-glucuronidase-estrogen metabolism-breast cancer axis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Kai-Wen Cheng, Chih-Hua Tseng, I. -Ju Chen, Bo-Cheng Huang, Hui-Ju Liu, Kai-Wen Ho, Wen-Wei Lin, Chih-Hung Chuang, Ming-Yii Huang, Yu-Lin Leu, Steve R. Roffler, Jaw-Yuan Wang, Yeh-Long Chen, Tian-Lu Cheng
Summary: The bidirectional interaction between gut microbiota and carcinogens in colorectal cancer is complex. Inhibition of microbial beta-glucuronidase (beta G) by TCH-3511 decreases AOM-induced gut microbial dysbiosis and intestinal tumorigenesis, suggesting the chemoprotective benefit of beta G inhibition in maintaining gut microbiota balance and preventing cancer-associated gut microbial dysbiosis.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Obstetrics & Gynecology
Yajing Wei, Hao Tan, Ruyu Yang, Fan Yang, Duo Liu, Biqi Huang, Linglong Ouyang, Shuntian Lei, Zehai Wang, Shaoru Jiang, Heng Cai, Xiaofei Xie, Shuzhong Yao, Yanchun Liang
Summary: This study explored the role of gut dysbiosis-derived beta-glucuronidase (GUSB) in the development of endometriosis. By sequencing stool samples from women with and without endometriosis, as well as a mouse model, it was found that beta-glucuronidase had higher expression in bowel lesions and uterosacral ligament lesions. Experimental results showed that beta-glucuronidase promoted the development of endometriosis, possibly by causing macrophage dysfunction.
FERTILITY AND STERILITY
(2023)
Review
Biochemistry & Molecular Biology
Sandica Bucurica, Mihaela Lupanciuc, Florentina Ionita-Radu, Ion Stefan, Alice Elena Munteanu, Daniela Anghel, Mariana Jinga, Elena Laura Gaman
Summary: Hepatocellular adenomas are benign liver tumors mostly associated with female users of estrogen-containing medications. The exact factors leading to the development of hepatic adenomas in certain females are still unknown. In addition, the conventional profile of individuals prone to hepatic adenoma is changing, with male patients exhibiting a higher risk of malignant progression. This paper theorizes the role of gut microbiota and beta-glucuronidase enzymes in the development of hepatic adenomas through the estrogen recycling pathway, aiming to address existing knowledge gaps and potential research areas.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Xiang-Ge Tian, Jian-Kun Yan, Cheng-Peng Sun, Jing-Xin Li, Jing Ning, Chao Wang, Xiao-Kui Huo, Wen-Yu Zhao, Zhen-Long Yu, Lei Feng, Xia Lv, Xiao-Chi Ma
Summary: The study revealed the inhibitory effects of Selaginella tamariscina and its major biflavonoid amentoflavone (AMF) on gut bacterial beta-glucuronidase (GUS), indicating their potential clinical utility in treating drug-induced enteropathy. The inhibitory activity of AMF against GUS was demonstrated through IC50 values and inhibition kinetics studies, with molecular docking and dynamics simulation providing insight into the mechanism of action. These findings suggest a promising approach in alleviating drug-induced gastrointestinal toxicity.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Multidisciplinary Sciences
Marine P. M. Letertre, Aadra P. Bhatt, Michael Harvey, Jeremy K. Nicholson, Ian D. Wilson, Matthew R. Redinbo, Jonathan R. Swann
Summary: Selective bacterial beta-glucuronidase inhibitors have a modulatory effect on gut microbial metabolism without adversely impacting the host metabolic system.
SCIENTIFIC REPORTS
(2022)
Review
Gastroenterology & Hepatology
Shiwan Hu, Qiyou Ding, Wei Zhang, Mengjiao Kang, Jing Ma, Linhua Zhao
Summary: A growing body of evidence supports the important role of gut microbiota in the reproductive endocrine system of women. Gut microbial beta-glucuronidase (gmGUS) is a key regulator of host estrogen metabolism, which is also influenced by estrogen levels. Disruptions in gmGUS-estrogen crosstalk and gut microbial dysbiosis can lead to estrogen-related diseases. This review highlights the regulatory role of gmGUS in estrogen metabolism, the interaction between gmGUS and estrogen, and the potential mechanisms behind them. Furthermore, gmGUS may serve as a potential biomarker for early diagnosis and treatment of estrogen-induced diseases.
Article
Biochemistry & Molecular Biology
Kento Sawane, Takahiro Nagatake, Koji Hosomi, Jun Kunisawa
Summary: Phytoestrogens have important roles in regulating the endocrine system and inflammatory metabolic disorders. The effects of dietary phytoestrogens on allergic diseases and their underlying mechanisms are still unclear. This study demonstrated that dietary secoisolariciresinol diglucoside (SDG), a phytoestrogen abundant in flaxseed, alleviated allergic rhinitis by microbial conversion to enterodiol (ED). The study also revealed that ED circulated mainly in the glucuronide form (EDGlu) in the blood and was deconjugated to ED aglycone in the nasal passage, with enhanced activity after the induction of allergic rhinitis mediated by beta-glucuronidase. Furthermore, ED aglycone inhibited IgE-mediated degranulation in a G protein-coupled receptor 30 (GPR30)-dependent manner. These findings provide new insights into the anti-allergic properties of phytoestrogens and their in vivo metabolism for the development of novel therapeutic strategies against allergic rhinitis.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Panpan Wang, Rongrong Wu, Yifei Jia, Puipui Tang, Bin Wei, Qingwen Zhang, Vivien Ya-Fan Wang, Ru Yan
Summary: This study evaluated the effects of twenty-one dietary flavones using three different taxonomic origins of Loop 1-type GUSs, revealing varied preferences and potential for tailoring inhibition based on specific GUS structure in the future.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Microbiology
Francesco Candeliere, Stefano Raimondi, Raffaella Ranieri, Eliana Musmeci, Alfonso Zambon, Alberto Amaretti, Maddalena Rossi
Summary: GUS enzymes produced by intestinal bacteria can affect the metabolism of drugs and xenobiotics by removing glucuronic acid from glucuronides. The number and structural categories of GUS enzymes vary in the gut microbiomes of different geographical populations, but they do not have significant correlations with drug response. L1 and mL1 are the most important categories of GUS enzymes involved in the hydrolysis of small molecules, with Bacteroides being a major contributor. Interindividual variations in GUS profiles, particularly in the L1 and mL1 categories, likely play a major role in the variability of pharmacomicrobiomics, which can influence drug response and toxicity.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biophysics
Yunlei Xianyu, Shixuan Su, Jing Hu, Ting Yu
Summary: This study introduces a novel approach for detecting beta-glucuronidase activity by modulating the silver mirror reaction on gold nanostars, leading to a significant change in surface plasmon resonance. This plasmonic nanosensor shows great promise for enzyme detection with a detection limit as low as 0.1 U/L.
BIOSENSORS & BIOELECTRONICS
(2021)
Article
Plant Sciences
Caiyan Wang, Xiaojun Teng, Chuang Wang, Binjie Liu, Runze Zhou, Huawei Qiu, Yu Fu, Rongjin Sun, Zuhui Liang, Rong Zhang, Zhongqiu Liu, Lin Zhang, Lijun Zhu
Summary: In this study, it was demonstrated that Xiao-Chai-Hu-Tang (XCHT) can alleviate CPT-11-induced diarrhea by improving the abundance of beneficial gut microbiota and reducing inflammation.
Article
Biochemistry & Molecular Biology
Obaidurahman Abid, Syahrul Imran, Muhammad Taha, Nor Hadiani Ismail, Waqas Jamil, Syed Muhammad Kashif, Khalid Mohammed Khan, Juliana Yusoff
Summary: In this study, a series of bisindolymethane hydrazone derivatives were synthesized and evaluated for in vitro beta-glucuronidase inhibitory activity. Several compounds exhibited potent inhibitory activity, with the presence of a hydroxyl group on the aromatic side chain being a major contributing factor. Docking studies predicted significant binding interactions between the active compounds and essential residues of beta-glucuronidase.
MOLECULAR DIVERSITY
(2021)
Article
Multidisciplinary Sciences
Aadra P. Bhatt, Samuel J. Pellock, Kristen A. Biernat, William G. Walton, Bret D. Wallace, Benjamin C. Creekmore, Marine M. Letertre, Jonathan R. Swann, Ian D. Wilson, Jose R. Roques, David B. Darr, Sean T. Bailey, Stephanie A. Montgomery, Jeffrey M. Roach, M. Andrea Azcarate-Peril, R. Balfour Sartor, Raad Z. Gharaibeh, Scott J. Bultman, Matthew R. Redinbo
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Chemistry, Multidisciplinary
Gina L. Morgan, Bo Li
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2020)
Article
Biochemistry & Molecular Biology
Ashley M. Kretsch, Gina L. Morgan, Katie A. Acken, Sarah A. Barr, Bo Li
Summary: Cell-to-cell communication via chemical signals is crucial for pathogenic bacteria to coordinate group behaviors and enhance virulence. The Pseudomonas virulence factor (pvf) gene cluster, found in over 500 proteobacteria strains, plays a key role in regulating gene expression, toxin production, and secondary metabolites through quorum sensing. The wide-ranging effects of PVF autoinducers suggest multifaceted roles in controlling cell physiology and promoting virulence, with implications for agriculturally and medically significant bacteria.
ACS CHEMICAL BIOLOGY
(2021)
Review
Clinical Neurology
Benjamin C. Creekmore, Yi-Wei Chang, Edward B. Lee
Summary: Neurodegenerative diseases are characterized by the accumulation of misfolded proteins. Studying protein regulation mechanisms can help reveal the pathophysiology of neurodegenerative diseases and offer new therapeutic opportunities.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2021)
Correction
Biochemistry & Molecular Biology
Ashley M. Kretsch, Gina L. Morgan, Katie A. Acken, Sarah A. Barr, Bo Li
ACS CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Rachel A. Johnson, Andrew N. Chan, Ryan D. Ward, Caylie A. McGlade, Breanne M. Hatfield, Jason M. Peters, Bo Li
Summary: Hybrid antibiotics like thiomarinol A show promise in combating antibiotic resistance, with a dual mode of action targeting IleRS and potentially involving metal chelation. Thiomarinol A remains effective against high-level mupirocin-resistant MRSA and shows less resistance development compared to mupirocin, emphasizing the importance of hybridity between DTP and mupirocin for potent activity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Gina L. Morgan, Kelin Li, Drake M. Crawford, Jeffrey Aube, Bo Li
Summary: Nonribosomal peptide synthetases (NRPSs) are enzyme complexes that play a crucial role in synthesizing complex natural products in bacteria. In this study, a monomodular NRPS enzyme PvfC was identified, which is essential for the production of various leucine-derived heterocyclic natural products, including novel signaling molecules and virulence factors. The discovery of a unique biosynthetic route involving PvfC expands our understanding of how bacteria generate diverse natural products.
ACS CHEMICAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jon B. Patteson, Andrew T. Putz, Lizhi Tao, William C. Simke, L. Henry Bryant, R. David Britt, Bo Li
Summary: The study reveals that Pseudomonas aeruginosa is able to synthesize a small-molecule copper complex, fluopsin C, in response to elevated copper concentrations, which serves as a broad-spectrum antibiotic. The pathway involves five enzymes and suggests a common role for fluopsin C in the copper stress response among various bacteria, highlighting its potential as an antibiotic against other microbes.
Article
Chemistry, Multidisciplinary
Jon B. Patteson, Camille Marie Fortinez, Andrew T. Putz, Juan Rodriguez-Rivas, L. Henry Bryant, Kamal Adhikari, Martin Weigt, T. Martin Schmeing, Bo Li
Summary: Dehydroamino acids are important in natural product synthesis, but the biosynthesis mechanism is not well understood. A unique class of condensation domains (C-modAA) has been found to play a role in dehydroamino acid biosynthesis, supported by biochemical and bioinformatic evidence. The crystal structure of a C-modAA domain has been obtained, which is involved in the synthesis of the antibiotic methoxyvinylglycine.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Adam R. Lescallette, Zachary D. Dunn, Viola A. Manning, Kristin M. Trippe, Bo Li
Summary: 4-Formylaminooxyvinylglycine (FVG) is a herbicidal and antibacterial nonproteinogenic amino acid produced by Pseudomonas fluorescens. The biosynthetic origin of FVG and two related O-N bond-containing oxyvinylglycines has been identified, and a formyltransferase enzyme (gvgI) required for FVG production has been characterized. This study provides insights into the biosynthesis of FVG and other related compounds.
Article
Chemistry, Physical
Xiaoyan Chen, Rachel M. Johnson, Bo Li
Summary: Amide N-methylation is crucial for the activity and permeability of bioactive compounds. This study identifies the amide N-methyltransferase DtpM, which converts holomycin to thiolutin, expanding the examples of amide N-methyltransferases and potentially enabling the synthesis of diverse dithiolopyrrolone compounds for therapeutics.
Article
Multidisciplinary Sciences
Katie A. Acken, Bo Li
Summary: Quorum sensing is a communication strategy used by bacteria to alter gene expression in response to cell density. The Pvf gene cluster regulates the production of secreted proteins and small molecules in the insect pathogen Pseudomonas entomophila L48. Additionally, Pvf controls multiple virulence mechanisms and biosynthetic gene clusters in P. entomophila L48.
Article
Biochemical Research Methods
Qiang Guo, Xiaoyan Chen, Bo Li
Summary: Polyamines are crucial for plant growth and survival. We studied the biochemical properties of SlADC1, an arginine decarboxylase enzyme, and explored its potential as a target for the bacterial small molecule phevamine A. Our results show that SlADC1 activity depends on the cofactor pyridoxal 5'-phosphate, has specificity towards L-arginine, and is competitively inhibited by phevamine A. This study provides a foundation for further inhibition studies of SlADC1.
PROTEIN EXPRESSION AND PURIFICATION
(2023)
Article
Biochemistry & Molecular Biology
Andrew N. N. Chan, Xiaoyan Chen, Julia A. Falco, Daniel W. Bak, Eranthie Weerapana, Bo Li
Summary: The natural product holomycin is a broad-spectrum antimicrobial compound that disrupts metal homeostasis through chelation of metal ions. It inhibits the activity of zinc-dependent and iron-sulfur cluster-dependent enzymes, inducing zinc and iron starvation in bacterial cells. This study highlights the potential of using chemoproteomics to investigate the impact of metal-binding molecules on metalloproteomes.
ACS CHEMICAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Xiaoyan Chen, Bo Li
Summary: Living organisms have developed various strategies to incorporate sulfur and selenium into bioactive natural products, many of which are essential medicines against infectious diseases and cancer. This review focuses on recent advances in the biosynthesis of sulfur/selenium-containing natural products, with an emphasis on the formation or cleavage of C-S/C-Se bonds. Unusual enzymes that catalyze these transformations are highlighted, their proposed mechanisms are described, and the potential for discovering and synthesizing novel natural products containing sulfur or selenium is discussed.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)