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S-Adenosylmethionine (SAM) is one of the most common co-substrates in enzyme-catalyzed methylation reactions. Most SAM-dependent reactions proceed through an SN2 mechanism, whereas a subset of them involves radical intermediates for methylating non-nucleophilic substrates. Herein, we report the characterization and mechanistic investigation of NosN, a class C radical SAM methyltransferase involved in the biosynthesis of the thiopeptide antibiotic nosiheptide. We show that, in contrast to all known SAM-dependent methyltransferases, NosN does not produce S-adenosylhomocysteine (SAH) as a co-product. Instead, NosN converts SAM into 5′-methylthioadenosine as a direct methyl donor, employing a radical-based mechanism for methylation and releasing 5′-thioadenosine as a co-product. A series of biochemical and computational studies allowed us to propose a comprehensive mechanism for NosN catalysis, which represents a new paradigm for enzyme-catalyzed methylation reactions. [ABSTRACT FROM AUTHOR]

The presence of malignant tumors poses a significant threat to people's life and well-being. As biochemical parameters indicate the occurrence and development of tumors, tumor markers play a pivotal role in early cancer detection, treatment, prognosis, efficient monitoring, and other aspects. Surface-enhanced Raman scattering (SERS) is considered a potent tool for the detection of tumor markers owing to its exceptional advantages encompassing high sensitivity, superior selectivity, rapid analysis speed, and photobleaching resistance nature. This review aims to provide a comprehensive understanding of SERS applications in the detection of tumor markers. Firstly, we introduce the SERS enhancement mechanism, classification of active substrates, and SERS detection techniques. Secondly, the latest research progress of in vitro SERS detection of different types of tumor markers in body fluids and the application of SERS imaging in biomedical imaging are highlighted in sections of the review. Finally, according to the current status of SERS detection of tumor markers, the challenges and problems of SERS in biomedical detection are discussed, and insights into future developments in SERS are offered. [Display omitted] • The SERS enhancement mechanism and SERS active substrates are overviewed. • SERS detection methods are classified as labeled-free and labeled detection. • The latest research progress of SERS in various tumor markers is discussed. • The challenges and perspectives concerning SERS technology are discussed. [ABSTRACT FROM AUTHOR]

Cancer has a high incidence and lethality rate, which is a significant threat to human health. With the development of high-throughput technologies, different types of cancer genomics data have been accumulated, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics. A comprehensive analysis of various omics data is needed to understand the underlying mechanisms of tumor development. However, integrating such a massive amount of data is one of the main challenges today. Artificial intelligence (AI) techniques such as machine learning are now becoming practical tools for analyzing and understanding multi-omics data on diseases. Enabling great optimization of existing research paradigms for cancer screening, diagnosis, and treatment. In addition, intelligent healthcare has received widespread attention with the development of healthcare informatization. As an essential part of innovative healthcare, practical, intelligent prognosis analysis and personalized treatment for cancer patients are also necessary. This paper introduces the advanced multi-omics data analysis technology in recent years, presents the cases and advantages of the combination of both omics data and AI applied to cancer diseases, and finally briefly describes the challenges faced by multi-omics analysis and AI at the current stage, aiming to provide new perspectives for oncology research and the possibility of personalized cancer treatment., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Sactionine-containing antibiotics (sactibiotics) are a growing class of peptide antibiotics belonging to the ribosomally synthesized and post-translationally modified peptide (RiPP) superfamily. We report the characterization of thuricin Z, a novel sactibiotic from Bacillus thuringiensis. Unusually, the biosynthesis of thuricin Z involves two radical S-adenosylmethionine (SAM) enzymes, ThzC and ThzD. Although ThzC and ThzD are highly divergent from each other, these two enzymes produced the same sactionine ring in the precursor peptide ThzA in vitro. Thuricin Z exhibits narrow-spectrum antibacterial activity against Bacillus cereus. A series of analyses, including confocal laser scanning microscopy, ultrathin-sectioning transmission electron microscopy, scanning electron microscopy, and large-unilamellar-vesicle-based fluorescence analysis, suggested that thuricin Z binds to the bacterial cell membrane and leads to membrane permeabilization., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

HemN is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the oxidative decarboxylation of coproporphyrinogen III to produce protoporphyrinogen IX, an intermediate in heme biosynthesis. HemN binds two SAM molecules in the active site, but how these two SAMs are utilized for the sequential decarboxylation of the two propionate groups of coproporphyrinogen III remains largely elusive. Provided here is evidence showing that in HemN catalysis a SAM serves as a hydrogen relay which mediates a radical-based hydrogen transfer from the propionate to the 5'-deoxyadenosyl (dAdo) radical generated from another SAM in the active site. Also observed was an unexpected shunt product resulting from trapping of the SAM-based methylene radical by the vinyl moiety of the mono-decarboxylated intermediate, harderoporphyrinogen. These results suggest a major revision of the HemN mechanism and reveal a new paradigm of the radical-mediated hydrogen transfer in radical SAM enzymology., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

S-Adenosylmethionine (SAM) is one of the most common co-substrates in enzyme-catalyzed methylation reactions. Most SAM-dependent reactions proceed through an S N 2 mechanism, whereas a subset of them involves radical intermediates for methylating non-nucleophilic substrates. Herein, we report the characterization and mechanistic investigation of NosN, a class C radical SAM methyltransferase involved in the biosynthesis of the thiopeptide antibiotic nosiheptide. We show that, in contrast to all known SAM-dependent methyltransferases, NosN does not produce S-adenosylhomocysteine (SAH) as a co-product. Instead, NosN converts SAM into 5'-methylthioadenosine as a direct methyl donor, employing a radical-based mechanism for methylation and releasing 5'-thioadenosine as a co-product. A series of biochemical and computational studies allowed us to propose a comprehensive mechanism for NosN catalysis, which represents a new paradigm for enzyme-catalyzed methylation reactions., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Lanthipeptides are a growing class of ribosomally synthesized and posttranslationally modified peptide (RiPP) natural products. These compounds are widely distributed among taxonomically distant species, and their structures and biological activities are diverse, providing an important source for drug research and developement. In this review, we summarized the recent advances in the understanding of structure, classification, evolution and substrate-controlled biosynthetic mechanism of lanthipeptide, attempting to highlight the intriguing chemistry and enzymology in the biosynthesis of this growing family of natural products.