Publications by authors named "Hui Ming Ge"

Article Synopsis
  • - The study focuses on a newly discovered hybrid polyketide called spirocycline A, generated from a gene cluster that combines modular type I and type II polyketide synthases (PKSs) alongside KAS III enzymes, which is a rare occurrence in bacterial aromatic polyketides.
  • - Spirocycline A's unique structure includes a distinct starter unit, four spirocycles, and a dimer formation, differentiating it from existing aromatic polyketides.
  • - The biosynthesis involves a collaborative effort where the type I PKS synthesizes the starter unit, which is then processed by KAS III and type II PKS to create the aromatic backbone, followed by further modifications by specific redox
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Article Synopsis
  • * This text highlights recent advances in understanding the enzymatic processes, specifically cyclization and oxidation, that are crucial for polyketide biosynthesis.
  • * The authors aim to inspire further research into these enzymatic mechanisms and encourage the discovery of new polyketide compounds through genome mining techniques.
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  • A new strain of fungus, Neopestalotiopsis clavispora AL01, was isolated from the leaf spots of date palms and produced six new secondary metabolites along with 11 known compounds during chemical analysis.
  • The structures of these compounds were identified using advanced techniques like NMR spectroscopy and mass spectrometry.
  • Some of the compounds showed phytotoxic effects on tobacco plants, while one exhibited weak antibacterial activity against certain resistant bacteria, paving the way for further research on beneficial natural products from fungi that affect plants.
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Cinnamoyl-containing nonribosomal peptides (CCNPs) constitute a unique family of actinobacterial secondary metabolites that display a broad spectrum of biological activities. Here, we present a genome mining approach targeting cyclase and is isomerase to discover new CCNPs, which led to the identification of 207 putative CCNP gene clusters from public bacterial genome databases. After strain prioritization, a novel class of CCNP-type glycopeptides named malacinnamycin was identified.

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Cyclic peptides with cyclophane linkers are an attractive compound type owing to the fine-tuned rigid three-dimensional structures and unusual biophysical features. Cytochrome P450 enzymes are capable of catalyzing not only the C-C and C-O oxidative coupling reactions found in vancomycin and other nonribosomal peptides (NRPs), but they also exhibit novel catalytic activities to generate cyclic ribosomally synthesized and post-translationally modified peptides (RiPPs) through cyclophane linkage. To discover more P450-modified multicyclic RiPPs, we set out to find cryptic and unknown P450-modified RiPP biosynthetic gene clusters (BGCs) through genome mining.

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Cyclization of linear peptides is an effective strategy to convert flexible molecules into rigid compounds, which is of great significance for enhancing the peptide stability and bioactivity. Despite significant advances in the past few decades, Nature and chemists' ability to macrocyclize linear peptides is still quite limited. P450 enzymes have been reported to catalyze macrocyclization of peptides through cross-linkers between aromatic amino acids with only three examples.

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Phomactin diterpenoids possess a unique bicyclo[9.3.1]pentadecane skeleton with multiple oxidative modifications, and are good platelet-activating factor (PAF) antagonists that can inhibit PAF-induced platelet aggregation.

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The objectives of this study were (1) to investigate the effect of extracts from some plants in the families Nelumbonaceae and Nymphaeaceae on phosphodiesterase 5 (PDE5) and arginase, which have been used in erectile dysfunction treatment, and (2) to isolate and identify the compounds responsible for such activities. The characterization and quantitative analysis of flavonoid constituents in the active extracts were performed by HPLC. Thirty-seven ethanolic extracts from different parts of plants in the genus and of Nymphaeaceae and genus of Nelumbonaceae were screened for PDE5 and arginase inhibitory activities.

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Terpenoids comprise the most chemically and structurally diverse family of natural products. In contrast to the huge numbers of terpenoids discovered from plants and fungi, only a relatively small number of terpenoids were reported from bacteria. Recent genomic data in bacteria suggest that a large number of biosynthetic gene clusters encoding terpenoids remain uncharacterized.

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Flavoprotein monooxygenases (FPMOs) play important roles in generating structural complexity and diversity in natural products biosynthesized by type II polyketide synthases (PKSs). In this study, we used genome mining to discover novel mutaxanthene analogues and investigated the biosynthesis of these aromatic polyketides and their unusual xanthene framework. We determined the complete biosynthetic pathway of mutaxathene through in vivo gene deletion and in vitro biochemical experiments.

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Tetracyclines are a class of antibiotics that exhibited potent activity against a wide range of Gram-positive and Gram-negative bacteria, yet only five members were isolated from actinobacteria, with two of them approved as clinical drugs. In this work, we developed a genome mining strategy using a TetR/MarR-transporter, a pair of common resistance enzymes in tetracycline biosynthesis, as probes to find the potential tetracycline gene clusters in the actinobacteria genome database. Further refinement using the phylogenetic analysis of chain length factors resulted in the discovery of 25 distinct tetracycline gene clusters, which finally resulted in the isolation and characterization of a novel tetracycline, hainancycline (1).

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Focusing on the cycloadditions, which have been widely utilized in total synthesis, this perspective reviews the flourish research of pericyclase for cycloaddition and discusses existing challenges.

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Lorneic acid and related natural products are characterized by a trialkyl-substituted benzene ring. The formation of the aromatic core in the middle of the polyketide chain is unusual. We characterized a cytochrome P450 enzyme that can catalyze the hallmark benzene ring formation from an acyclic polyene substrate through genetic and biochemical analysis.

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Six new (1-6) and seven known depsidones (7-13) were isolated from the culture of an ant (Monomorium chinensis)-derived fungus Spiromastix sp. MY-1. Their structures were elucidated by extensive spectroscopic analysis including high resolution MS, 1D and 2D NMR data.

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Macrocyclization is an important process that affords morphed scaffold in biosynthesis of bioactive natural products. Nature has adapted diverse biosynthetic strategies to form macrocycles. In this work, we report the identification and characterization of a small enzyme AvmM that can catalyze the construction of a 16-membered macrocyclic ring in the biosynthesis of alchivemycin A (1).

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Article Synopsis
  • * The study outlines the biosynthesis of sordarin, starting with a diterpene cyclase (SdnA) that creates a specific cycloaraneosene framework, which is then modified through a series of oxidation reactions by P450 enzymes.
  • * A novel enzyme known as Diels-Alderase SdnG plays a crucial role in forming the sordarin core structure through an intramolecular Diels-Alder reaction, followed by additional modifications like methyl hydroxylation
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Spirocitromycetin, an antiosteoporotic polyketide bearing a unique spirocycle, was characterized from a human mucus sputum-derived . Its structure and absolute configuration were elucidated spectrally, with its biosynthetic pathway likely mediated via polivione, a reported heptaketide. Spirocitromycetin was shown to be antiosteoporotic at 0.

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Cinnamoyl-containing natural products (CCNPs) are a small class of bacterial metabolites with notable bioactivities. The biosynthesis of cinnamoyl moiety has been proposed to be assembled by an unusual highly reducing (HR) type II polyketide synthases (PKS). However, the biosynthetic route, especially the cyclization step for the benzene ring formation, remains unclear.

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Article Synopsis
  • The enzyme NgnD catalyzes a cycloaddition reaction that produces two types of products: [6+4] and [4+2] adducts, but how the enzyme and water affect the selection of these products is still unclear.
  • Researchers used quantum mechanics and molecular dynamics simulations alongside biochemical tests to investigate how water and the enzyme influence the reactions after the transition state.
  • The findings show that the proportions of the two products change significantly in different environments (gas, water, enzyme), highlighting the important role of water and enzyme in determining the selectivity of chemical reactions at extremely fast timescales (femtoseconds).
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Redox tailoring enzymes play key roles in generating structural complexity and diversity in type II polyketides. In chartreusin biosynthesis, the early C-labeling experiments and bioinformatic analysis suggest the unusual aglycone is originated from a tetracyclic anthracyclic polyketide. Here, we demonstrated that the carbon skeleton rearrangement from a linear anthracyclic polyketide to an angular pentacyclic biosynthetic intermediate requires two redox enzymes.

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The solid-state cultivation of sp. H-JQSF isolated from produces acautalides A-C (-) as skeletally unprecedented Diels-Alder adducts of a 14-membered macrodiolide to an octadeca-9,11,13-trienoic acid. The acautalide structures, along with the intramolecular transesterifications of 1-acylglycerols, were elucidated by mass spectrometry, nuclear magnetic resonance, chemical transformation, and single-crystal X-ray diffraction.

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Nonribosomal peptide synthetases (NRPSs) are modular enzymes that use a thiotemplate mechanism to assemble the peptide backbones of structurally diverse and biologically active natural products in bacteria and fungi. Unlike these canonical multi-modular NRPSs, single-module NRPS-like enzymes, which lack the key condensation (C) domain, are rare in bacteria, and have been largely unexplored to date. Here, we report the discovery of a gene cluster () encoding a NRPS-like megasynthetase through genome mining.

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Nonribosomal peptides (NRPs) that are synthesized by modular megaenzymes known as nonribosomal peptide synthetases (NRPSs) are a rich source for drug discovery. By targeting an unusual NRPS architecture, we discovered an unusual biosynthetic gene cluster () from sp. 120454 and identified that it was responsible for the biosynthesis of a series of novel linear peptides, bosamycins.

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Ansaseomycins are ansamycin-type natural products produced through expression of the gene cluster in a heterologous host. A rare berberine bridge enzyme (BBE) like oxidase, AsmF, is encoded in the gene cluster. Deletion of led to the accumulation of a series of structurally diverse compounds, all of which lacked the 23-hydroxyl group in naphthalenic motif.

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