Surface-enhanced Raman scattering-based strategies for tumor markers detection: A review.

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.

Programmable and ultra-efficient Argonaute protein-mediated nucleic acid tests: A review.

With the attributes of high sensitivity, single-base resolution, multiplex detection capability, and programmability upon nucleic acid recognition, Argonaute (Ago)-based biosensing assays are increasingly recognized as one of the most promising tools for precise identification and quantification of target analytes. Employed as highly specific sequence recognition elements of these robust diagnostic methods, Agos are revolutionizing how nucleic acid targets are detected. A systematic and comprehensive summary of this emerging and rapid-advancing technology is necessary to give play to the potential of Ago-based biosensing assays.

Towards new bioactive fluorine-containing 1,3,4-oxadiazole-amide derivatives: synthesis, antibacterial activity, molecular docking and molecular dynamics simulation study.

Through the approach of molecular hybridization, this study rationally designed and synthesized new trifluoromethyl-1,3,4-oxadiazole amide derivatives, denoted as 1a-1n. The findings reveal that these novel molecules exhibit potent inhibitory effects against various bacterial strains. Thereinto, compounds 1c, 1d, 1i, 1j and 1n, demonstrate relatively superior antimicrobial performance against B.

Combination of nucleic acid amplification and CRISPR/Cas technology in pathogen detection.

Major health events caused by pathogenic microorganisms are increasing, seriously jeopardizing human lives. Currently PCR and ITA are widely used for rapid testing in food, medicine, industry and agriculture. However, due to the non-specificity of the amplification process, researchers have proposed the combination of nucleic acid amplification technology with the novel technology CRISPR for detection, which improves the specificity and credibility of results.

A gene-encoded aldehyde tag repurposed from RiPP cyclophane-forming pathway.

Gene-encoded aldehyde tag technology has been widely utilized in protein bioorthogonal chemistry and biotechnological application. Herein, we report utilization of the promiscuous rSAM cyclophane synthase SjiB involved in triceptide biosynthesis as a dedicated and highly efficient formylglycine synthase. The new aldehyde tag sequence in this system, YQSSI, is biosynthetically orthogonal to the known aldehyde tag (C/S)x(P/A)xR.

Substrate-Controlled Catalysis in the Ether Cross-Link-Forming Radical SAM Enzymes.

Darobactin is a heptapeptide antibiotic featuring an ether cross-link and a C-C cross-link, and both cross-links are installed by a radical S-adenosylmethionine (rSAM) enzyme DarE. How a single DarE enzyme affords the two chemically distinct cross-links remains largely obscure. Herein, by mapping the biosynthetic landscape for darobactin-like RiPP (daropeptide), we identified and characterized two novel daropeptides that lack the C-C cross-link present in darobactin and instead are solely composed of ether cross-links.

The gut microbiome in human health and disease-Where are we and where are we going? A bibliometric analysis.

Background: There are trillions of microbiota in our intestinal tract, and they play a significant role in health and disease interacting with the host in metabolic, immune, neural, and endocrine pathways. Over the past decades, numerous studies have been published in the field of gut microbiome and disease. Although there are narrative reviews of gut microbiome and certain diseases, the whole field is lack of systematic and quantitative analysis.

Hijacking a Linaridin Biosynthetic Intermediate for Lanthipeptide Production.

Linaridins and lanthipeptides are two classes of natural products belonging to the ribosomally synthesized and posttranslationally modified peptide (RiPP) superfamily. Although these two RiPP classes share similar structural motifs such as dehydroamino acids and thioether-based cross-links, the biosynthesis of linaridins and lanthipeptides involved distinct sets of enzymes. Here, we report the identification of a novel lanthipeptide cypepeptin from a recombinant strain of , which harbors most of the cypemycin (a prototypic linaridin) biosynthetic gene cluster but lacks the decarboxylase gene .

Dissection of the Glycosylation in the Biosynthesis of the Heptadecaglycoside Antibiotic Saccharomicin A.

Oligosaccharide natural products have diverse biological activities and represent a potentially important source for drug development. In this study, we focus on the glycosylation pathway in the biosynthesis of saccharomicin A (SA-A), an oligosaccharide antibiotic containing 17 sugar moieties. By extensive gene-knockout studies with comparative metabolic profile analysis, we established a complete pathway in assembling the heptadecasaccharide chain of SA-A, the longest saccharide chain found in natural products.

Thuricin Z: A Narrow-Spectrum Sactibiotic that Targets the Cell Membrane.

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.

Movements of the Substrate-Binding Clamp of Cypemycin Decarboxylase CypD.

Linaridins are a small but growing class of natural products belonging to the ribosomally synthesized and post-translationally modified peptide (RiPP) superfamily. The class A linaridins, exemplified by cypemycin, possess an unusual S-[( Z)-2-aminovinyl]-d-cysteine (AviCys) residue. Formation of the AviCys in cypemycin requires an oxidative decarboxylation of the precursor peptide C-terminal Cys, and this reaction is catalyzed by a flavin-dependent decarboxylase CypD.

Revisiting the Mechanism of the Anaerobic Coproporphyrinogen III Oxidase HemN.

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.

Convergent evolution of the Cys decarboxylases involved in aminovinyl-cysteine (AviCys) biosynthesis.

S-[(Z)-2-aminovinyl]-d-cysteine (AviCys) is a unique motif found in several classes of ribosomally synthesized and post-translationally modified peptides (RiPPs). Biosynthesis of AviCys requires flavin-dependent Cys decarboxylases, which are highly divergent among different RiPP classes. In this study, we solved the crystal structure of the cypemycin decarboxylase CypD.

Cypemycin Decarboxylase CypD Is Not Responsible for Aminovinyl-Cysteine (AviCys) Ring Formation.

The cypemycin decarboxylase CypD is investigated by using a synthetic oligopeptide, which contains the to-be-cyclized dehydroalanine (Dha) residue. It was shown that CypD efficiently catalyzes the decarboxylation of this Dha-containing peptide, but the expected AviCys ring is not formed in the product, suggesting that CypD alone is not enough to form the AviCys ring. It was also shown that the Dha-containing peptide is a better substrate than two similar peptides with a Ser or a Cys residue, supporting that, in cypemycin biosynthesis, Dha formation is prior to decarboxylation of the C-terminal Cys.

Substrate specificity of the cypemycin decarboxylase CypD.

The linaridin antibiotic cypemycin is a ribosomal synthesized and post-translationally modified peptide (RiPP) that possesses potent activity against mouse leukemia cells. This peptide natural product contains an -[()-2-aminovinyl]-d-cysteine (AviCys) moiety in the C-terminus. Formation of AviCys moiety requires an oxidative decarboxylation of the C-terminal Cys of the precursor peptide CypA, and this process is catalyzed by a flavin-containing protein CypD.

Biosynthesis of the nosiheptide indole side ring centers on a cryptic carrier protein NosJ.

Nosiheptide is a prototypal thiopeptide antibiotic, containing an indole side ring in addition to its thiopeptide-characteristic macrocylic scaffold. This indole ring is derived from 3-methyl-2-indolic acid (MIA), a product of the radical S-adenosylmethionine enzyme NosL, but how MIA is incorporated into nosiheptide biosynthesis remains to be investigated. Here we report functional dissection of a series of enzymes involved in nosiheptide biosynthesis.

A mechanistic study of the non-oxidative decarboxylation catalyzed by the radical S-adenosyl-l-methionine enzyme BlsE involved in blasticidin S biosynthesis.

Decarboxylation is a fundamentally important reaction in biology and involves highly diverse mechanisms. Here we report a mechanistic study of the non-oxidative decarboxylation catalyzed by BlsE, a radical S-adenosyl-l-methionine (SAM) enzyme involved in blasticidin S biosynthesis. Through a series of biochemical analysis with isotopically labeled reagents, we show that the BlsE-catalyzed reaction is initiated by the 5'-deoxyadenosyl (dAdo) radical-mediated hydrogen abstraction from a sugar carbon of the substrate cytosylglucuronic acid (CGA), and does not involve a carboxyl radical as has been proposed for 4-hydroxyphenylacetate decarboxylase (HPAD).

Biosynthetic Insights into Linaridin Natural Products from Genome Mining and Precursor Peptide Mutagenesis.

Linaridin is a small class of peptide natural products belonging to the ribosomally synthesized and post-translationally modified peptides (RiPPs) superfamily. By an extensive genome-wide survey of linaridin biosynthetic genes, we show that this class of natural products is widespread in nature and possesses vast structural diversity. The linaridin precursor peptides are relatively conserved in the N-termini but have diverse sequences in the core region, which appear to have coevolved with the biosynthetic enzymes.

The Catalytic Mechanism of the Class C Radical S-Adenosylmethionine Methyltransferase NosN.

S-Adenosylmethionine (SAM) is one of the most common co-substrates in enzyme-catalyzed methylation reactions. Most SAM-dependent reactions proceed through an S 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.

[Recent advances in lanthipeptide biosynthesis - A review].

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.

Metabolic flux analysis of the halophilic archaeon Haladaptatus paucihalophilus.

This work reports the (13)C-assisted metabolic flux analysis of Haladaptatus paucihalophilus, a halophilic archaeon possessing an intriguing osmoadaption mechanism. We showed that the carbon flow is through the oxidative tricarboxylic acid (TCA) cycle whereas the reductive TCA cycle is not operative in H. paucihalophilus.