Article
Biochemistry & Molecular Biology
Cheng-Jian Zheng, Edward Kalkreuter, Bo-Yi Fan, Yu-Chen Liu, Liao-Bin Dong, Ben Shen
Summary: This study presents a detailed investigation of PtmC, an unusual NAT homologue involved in the biosynthesis of thioplatensimycin and related compounds, highlighting its unique role and evolution from canonical NAT scaffold. The findings expand our understanding of enzyme evolution for substrate diversity and provide insights into the activities of NATs in natural product biosynthesis and xenobiotic detoxification.
ACS CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Ashley J. Winter, Matthew T. Rowe, Angus N. M. Weir, Nahida Akter, Sbusisiwe Z. Mbatha, Paul D. Walker, Christopher Williams, Zhongshu Song, Paul R. Race, Christine L. Willis, Matthew P. Crump
Summary: In this study, the remaining steps of 9HN biosynthesis were investigated using NMR spectroscopy, mass spectrometry, chemical probes, and in vitro assays. The results reveal a complex interplay between multiple acyl carrier proteins and a novel KS-AT didomain.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Plant Sciences
Samuel Scott, Edgar B. Cahoon, Lucas Busta
Summary: Plants have the ability to produce lineage-specific natural products from their core metabolic pathways. However, little attention has been given to natural products derived from fatty acids. Recent studies have shown that plants can produce structurally diverse compounds from fatty acids, some of which have unique structural features and novel functionalities. This review aims to summarize the current knowledge of fatty acid-derived natural products and their biosynthesis, and suggest future research priorities.
Article
Biochemistry & Molecular Biology
Shumpei Asamizu, Abrory Agus Cahya Pramana, Sung-Jin Kawai, Yoshichika Arakawa, Hiroyasu Onaka
Summary: In this study, a coculture method was used to investigate the potential for secondary metabolite biosynthesis by Streptomyces species. Specific antibacterial activity was discovered in a combined-culture of Streptomyces hygroscopicus HOK021 and Tsukamurella pulmonis TP-B0596. Molecular networking and genomic data analysis revealed the formation of a previously unidentified conjugate between FabF inhibitor and catechol-type siderophore, named harundomycin A. The study demonstrated the transformation of existing natural products to bifunctional molecules driven by bacterial interaction.
ACS CHEMICAL BIOLOGY
(2022)
Review
Engineering, Environmental
Adeyemi S. Adeleye, Jie Xue, Yixin Zhao, Alicia A. Taylor, Jenny E. Zenobio, Yian Sun, Ziwei Han, Omobayo A. Salawu, Yurong Zhu
Summary: Pharmaceuticals and personal care products (PPCPs) are commonly found in wastewater and the environment, primarily entering municipal wastewater systems through human excretion and also from hospitals, PPCPs manufacturers, and agriculture. The most abundant PPCPs in raw wastewater include analgesics, antibiotics, and stimulants. In conventional wastewater treatment plants, most removal of PPCPs occurs during secondary treatment, with an overall removal rate exceeding 90%.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
Review
Microbiology
Christopher D. Radka, Charles O. Rock
Summary: Antibiotic resistance is a significant public health concern, and developing new drugs targeting bacterial type II fatty acid synthesis (FASII) is a potential solution. However, there are obstacles in FASII drug development, and broad-spectrum drugs against FASII targets may be unlikely due to bacteria's ability to assimilate exogenous fatty acids. Pathogen-specific FASII drugs are considered the best option, but there is a risk of rapid resistance acquisition. Optimizing compound design during drug development can help mitigate this issue.
ANNUAL REVIEW OF MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ji Su Yang, Naeun Yoon, Mingyu Kong, Byung Hwa Jung, Hyunbeom Lee, Jinyoung Park
Summary: While attempts were made to inhibit cancer cell growth by combining FASN and USP14 inhibitors, there were no synergistic effects on cancer cell death compared to FASN inhibitor alone. Surprisingly, the USP14 inhibitor IU1 did not significantly affect FASN levels in cancer cells, and metabolite changes in IU1-treated cells differed significantly from those in cells treated with the FASN inhibitor Fasnall.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Raushanara Akter, Afrina Afrose, Md. Rashidur Rahman, Rakhi Chowdhury, Saif Shahriar Rahman Nirzhor, Rubayat Islam Khan, Md. Tanvir Kabir
Summary: Natural products have been traditionally used as drugs to treat a wide range of human diseases and have been important in the discovery of active compounds, biological activity patterns, and candidate drugs. SIRT6, a key gene involved in multiple diseases, can be modulated by natural compounds, offering potential for treatment and research of related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Suze Ma, Dhanaraju Mandalapu, Shu Wang, Qi Zhang
Summary: Cyclopropane has attracted wide interests in the fields of synthetic and pharmaceutical chemistry, and chemical biology due to its unique structural and chemical properties. Enzymatic cyclopropanations can be grouped into two major pathways based on reaction mechanism, and classified based on key intermediates required prior to cyclopropane formation. The study also emphasizes on the mechanism and engineering of enzymes necessary for forming this unique structure motif in natural products.
NATURAL PRODUCT REPORTS
(2022)
Article
Gastroenterology & Hepatology
Haichuan Wang, Yi Zhou, Hongwei Xu, Xue Wang, Yi Zhang, Runze Shang, Marie O'Farrell, Stephanie Roessler, Carsten Sticht, Andreas Stahl, Matthias Evert, Diego F. Calvisi, Yong Zeng, Xin Chen
Summary: This study evaluated the therapeutic efficacy of the FASN inhibitor TVB3664 for HCC treatment and found that it has limited effectiveness as monotherapy, but can be combined with other drugs for improved results. These combination therapies can be developed based on driver oncogenes, supporting precision medicine approaches for HCC treatment.
Article
Biochemistry & Molecular Biology
Ling Huang, Jun Zhang, Bo Wei, Shuangyang Chen, Sitong Zhu, Weiguan Qi, Xiaoying Pei, Lulu Li, Weiguang Liu, Yuzhi Wang, Xiaojun Xu, Lan-Gui Xie, Liming Chen
Summary: Lack of MHC-II is identified as a key factor in cancer immune evasion, and the development of small-molecule MHC-II inducers is essential. In this study, researchers discovered three MHC-II inducers that effectively induce MHC-II expression in breast cancer cells and inhibit the development of breast cancer. The findings suggest that MHC-II plays a central role in promoting immune detection of cancer and enhancing anti-cancer immunity by increasing T cell infiltration in tumors. The study also revealed that fatty acid-mediated MHC-II silencing is directly linked to immune detection evasion and cancer metabolic reprogramming.
CELL CHEMICAL BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Zhe Wang, Xingyun Liu, Yanwen Duan, Yong Huang
Summary: Research shows that hydrogels containing PTM nanoparticles can effectively treat skin infections caused by MRSA, not only exerting antibacterial effects but also accelerating wound healing, effectively treating subcutaneous tissue infections without toxicity.
MOLECULAR PHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Hanyuan Xu, Linjie Wang, Kemin Yan, Huijuan Zhu, Hui Pan, Hongbo Yang, Meijuan Liu, Fengying Gong
Summary: The study demonstrated that nuciferine has inhibitory effects on the proliferation and differentiation of 3T3-L1 preadipocytes, possibly through downregulation of PPARγ, C/EBPα, and C/EBPβ, which in turn affects the transcription of lipogenic enzymes and lipid accumulation. Additionally, nuciferine can promote the expression of adipokines in fully differentiated adipocytes.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Yueting Deng, Yang Liu, Juan Li, Xiao Wang, Shan He, Xiaojun Yan, Yutong Shi, Weiyan Zhang, Lijian Ding
Summary: Biofilm is a complex microbial consortium with resistance mechanisms to known antibiotics, posing a threat to human health. Marine organisms provide abundant resources for the development of anti-biofilm agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Anna-Kay R. West, Constance B. Bailey
Summary: The article discusses the interconnected biosynthesis between fatty acid synthases (FASs) and polyketide synthases (PKSs) in primary and secondary metabolism. Understanding the linkage between polyketide biosynthesis and fatty acid biosynthesis may lead to the discovery and production of novel drug leads from polyketide metabolites.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Caroline W. Karanja, Kofi S. Yeboah, Herman O. Sintim
Summary: Immune cells respond to bacterial and host-derived molecules to produce an immune response, while some pathogens can weaken host response through specific enzymes. Researchers have identified compounds that inhibit MTB CDN PDE, but there remains a lack of such specific inhibitors.
ACS INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
George A. Naclerio, Nader S. Abutaleb, Marwa Alhashimi, Mohamed N. Seleem, Herman O. Sintim
Summary: New N-(1,3,4-oxadiazol-2-yl)benzamides (HSGN-237 and HSGN-238) have been discovered as highly potent compounds against Neisseria gonorrhoeae, as well as clinically important Gram-positive bacteria, with outstanding tolerability to human cell lines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Zhichao Tang, Junxing Zhao, Zach J. Pearson, Zarko V. Boskovic, Jingxin Wang
Summary: RNA splicing is crucial in producing mature mRNA, and leveraging splicing modifiers as a pharmacological modality shows promising potential in treating diseases caused by aberrant splicing. Approved drugs include antisense oligonucleotide splicing modifiers and a small-molecule splicing modifier risdiplam, targeting mRNA precursors.
Article
Biochemistry & Molecular Biology
Zhichao Tang, Sana Akhter, Ankita Ramprasad, Xiao Wang, Mikhail Reibarkh, Jinan Wang, Sadikshya Aryal, Srinivas S. Thota, Junxing Zhao, Justin T. Douglas, Philip Gao, Erik D. Holmstrom, Yinglong Miao, Jingxin Wang
Summary: The study found that a known risdiplam analogue, SMN-C2, binds to single-stranded GA-rich RNA in a sequence-specific manner, with a minimum required binding sequence identified as GAAGGAAGG. Through simulations and experimental data, the research demonstrated the binding mechanism of small-molecule splicing modulators to target nucleic acids, revealing a novel binding mode.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Microbiology
Kenneth Onyedibe, Samira Elmanfi, Uma K. Aryal, Eija Kononen, Ulvi Kahraman Gursoy, Herman O. Sintim
Summary: This study reveals that cyclic dinucleotides (CDNs) derived from bacteria not only regulate cytokine production via STING, but also broadly affect many critical processes in human cells, including interferon signaling pathways and other not fully characterized pathways. This highlights the importance of understanding the response of human gingival fibroblasts to bacterial-derived CDNs.
JOURNAL OF ORAL MICROBIOLOGY
(2022)
Article
Chemistry, Medicinal
George A. Naclerio, Kenneth Onyedibe, Caroline W. Karanja, Uma K. Aryal, Herman O. Sintim
Summary: Drug-resistant bacterial pathogens continue to cause high mortality rates, necessitating new chemical modalities for treatment. Halogenated N-(1,3,4-oxadiazol-2-yl)benzamides are an interesting class of antimicrobial agents with multiple modes of action and low propensity for MRSA resistance development.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Medicinal
Neetu Dayal, Kenneth I. Onyedibe, Whitney M. Gribble, Herman O. Sintim
Summary: According to the National Institute of Health (NIH), the majority of human microbial infections are caused by bacterial biofilms and are resistant to FDA approved drugs. Therefore, there is a need for the development of antibiotics that can target biofilms. Researchers have synthesized pentafluorosulfanyl (SF5)-containing compounds and expanded the compounds in the library to discover potential therapeutics. The results showed that these compounds can effectively kill bacteria in biofilms without toxic effects on human cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Kenneth I. Onyedibe, Ansley M. Nemeth, Neetu Dayal, Richard D. Smith, Jones Lamptey, Robert K. Ernst, Roberta J. Melander, Christian Melander, Herman O. Sintim
Summary: Researchers have discovered a compound called HSD1624 that enhances the effectiveness of the antibiotic colistin against resistant bacteria in multiple strains.
ACS INFECTIOUS DISEASES
(2023)
Editorial Material
Chemistry, Multidisciplinary
Christopher Vennard, Herman O. Sintim
ACS CENTRAL SCIENCE
(2022)
Article
Oncology
Ujjwol Khatri, Neetu Dayal, Xueqing Hu, Elizabeth Larocque, Nimishetti Naganna, Tao Shen, Xuan Liu, Frederick W. Holtsberg, M. Javad Aman, Herman O. Sintim, Jie Wu
Summary: Selpercatinib and pralsetinib are approved RET kinase inhibitors for treating RET-altered cancers, but resistance mutations have been identified. This study investigates the sensitivities of different G810 mutants to these inhibitors and identifies new compounds for inhibiting resistant mutations.
MOLECULAR CANCER THERAPEUTICS
(2023)
Editorial Material
Chemistry, Medicinal
Christopher Vennard, Temitope Oropo, Herman O. Sintim
Summary: Vancomycin-like drugs target peptidoglycan by binding to the C-terminal d-Ala-d-Ala dipeptide. An engineered vancomycin with enhanced affinity for the peptidoglycan stem peptide, possibly through interactions with meso-diaminopimelic acid, displays increased killing of mycobacteria.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Allison L. Kempen, Nickolas R. Brauer, Herman O. Sintim
Summary: The study describes the synthesis of a newly discovered 3H-pyrazolo[4,3-f]quinoline core through a multi-component Doebner-Povarov reaction, which has the ability to selectively inhibit cancer-associated kinases FLT3 and haspin. The researchers report the discovery of a potent dual FLT3/haspin inhibitor, HSK205, which shows remarkable activity against FLT3-driven AML cell lines.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Wilson W. S. Ong, Neetu Dayal, Riddhi Chaudhuri, Jones Lamptey, Herman O. O. Sintim
Summary: The cGAS-STING axis is important in protecting higher organisms against pathogens or cancer. However, overactivation of this pathway can lead to inflammation, which is harmful to the host. STING antagonists, such as HSD1077, have been discovered and shown to inhibit STING binding, suppressing interferon expression and potentially managing various inflammatory diseases.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Desmond Akwata, Allison L. Kempen, Jones Lamptey, Neetu Dayal, Nickolas R. Brauer, Herman O. Sintim
Summary: Current treatment options for multiple myeloma patients are limited, and there is a need for effective targeted therapies. Recent studies have shown that the transforming growth factor-beta activated kinase (TAK1) is overexpressed in multiple myeloma, providing hope for the discovery of TAK1 inhibitors.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Desmond Akwata, Allison L. Kempen, Neetu Dayal, Nickolas R. Brauer, Herman O. Sintim
Summary: FLT3 is expressed in immune and cancer cells and has potential applications in the treatment of acute myeloid leukemia and chronic pain. However, current FLT3 inhibitors also inhibit other important kinases, which limits their use in non-oncology applications.
