A5001887570- Microbial Natural Products and Biosynthesis
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- CRISPR and Genetic Engineering
- Carbohydrate Chemistry and Synthesis
- Marine Sponges and Natural Products
- Chemical Synthesis and Analysis
- Plant-Microbe Interactions and Immunity
- Plant Disease Resistance and Genetics
- Enzyme Production and Characterization
- Bacterial Genetics and Biotechnology
- Biochemical and Molecular Research
- Microbial Metabolic Engineering and Bioproduction
- Advanced biosensing and bioanalysis techniques
- Insect symbiosis and bacterial influences
- RNA modifications and cancer
- Enzyme Catalysis and Immobilization
- Antimicrobial Peptides and Activities
- Metabolism and Genetic Disorders
- Synthetic Organic Chemistry Methods
- Plant biochemistry and biosynthesis
- Neurological diseases and metabolism
- Dyeing and Modifying Textile Fibers
- Fungal Biology and Applications
Wuhan University
2016-2025
Zhongnan Hospital of Wuhan University
2023-2025
Huazhong University of Science and Technology
2024-2025
Bengbu Medical College
2025
Shandong Normal University
2024
Ningbo University
2024
Beijing Forestry University
2024
Shanxi Province Hospital of Traditional Chinese Medicine
2024
Institut Universitaire de Cardiologie et de Pneumologie de Québec
2022
Aerospace Information Research Institute
2022
Abstract Background The alarming spread of antimicrobial resistance requires the development novel anti-infective drugs. Despite recent research focus on human microbiome and its likely value to understand exploit inter-bacterial inhibitory phenomena as a source for strategies, microbiota has barely been investigated purpose drug development. Results We performed large screen analyzing over 3000 skin isolates evaluate bacterial competition within basis therapeutics. discovered Staphylococcus...
Several independent gene clusters containing varying lengths of type I polyketide synthase genes were isolated from ‘Streptomyces nanchangensis’ NS3226, a producer nanchangmycin and meilingmycin. The former is polyether compound similar to dianemycin the latter macrolide milbemycin, which shares same ring as avermectin but has different side groups. Clusters A–H spanned about 133, 132, 104, 174, 122, 54, 37 59 kb, respectively. Two systems developed for functional analysis by disruption or...
Gentamicin C complex is a mixture of aminoglycoside antibiotics used worldwide to treat severe Gram-negative bacterial infections. Despite its clinical importance, the enzymology biosynthetic pathway has remained obscure. We report here insights into four enzyme-catalyzed steps that lead from first-formed pseudotrisaccharide gentamicin A2 X2, last common intermediate for all components complex. have both targeted mutations individual genes and reconstitution portions in vitro show secondary...
The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system, an RNA-guided nuclease for specific genome editing in vivo, has been adopted a wide variety of organisms. In contrast, the vitro application CRISPR/Cas9 system rarely reported. We present here highly efficient CRISPR/Cas9-mediated (ICE) that allows refactoring biosynthetic gene clusters Streptomyces bacteria and other large DNA fragments. Cleavage by Cas9 circular pUC18 was...
The soil-dwelling filamentous bacteria, Streptomyces, is widely known for its ability to produce numerous bioactive natural products. Despite many efforts toward their overproduction and reconstitution, our limited understanding of the relationship between host's chromosome three dimension (3D) structure yield products escaped notice. Here, we report 3D organization dynamics model strain, Streptomyces coelicolor, during different growth phases. undergoes a dramatic global structural change...
The biosynthetic gene cluster for tetronomycin (TMN), a polyether ionophoric antibiotic that contains four different types of ring, including the distinctive tetronic acid moiety, has been cloned from Streptomyces sp. NRRL11266. sequenced tmn locus (113 234 bp) six modular polyketide synthase (PKS) genes and further 27 open-reading frames. Based on sequence comparison to related clusters, majority these can be assigned plausible role in TMN biosynthesis. identity cluster, requirement number...
Gentamicin C complex from Micromonospora echinospora remains a globally important antibiotic, and there is revived interest in the semisynthesis of analogs that might show improved therapeutic properties. The consists five components differing their methylation pattern at one or more sites molecule. We here, using specific gene deletion chemical complementation, gentamicin pathway up to branch point defined by selectivity methyltransferases GenN, GenD1, GenK. Unexpectedly, they comprise...
Gentamicin C complex is a mixture of aminoglycoside antibiotics used to treat severe Gram-negative bacterial infections. We report here key features the late-stage biosynthesis gentamicins. show that intermediate gentamicin X2, known substrate for C-methylation at C-6' form G418 catalyzed by radical SAM-dependent enzyme GenK, may instead undergo oxidation an aldehyde, flavin-linked dehydrogenase GenQ. Surprisingly, GenQ acts in both branches pathway, likewise oxidizing analogous ketone....
Abstract Base editing (BE) faces protospacer adjacent motif (PAM) constraints and off-target effects in both eukaryotes prokaryotes. For Streptomyces , renowned as one of the most prolific bacterial producers antibiotics, challenges are more pronounced due to its diverse genomic content high GC content. Here, we develop a base editor named eSCBE3-NG-Hypa, tailored with efficiency -fidelity for . Of note, eSCBE3-NG-Hypa recognizes NG PAM exhibits activity at challenging sites or motifs, while...
The biosynthetic pathway to the unusual tetronate ring of certain polyketide natural products, including antibiotics abyssomicin and tetronomycin (TMN) antitumour compound chlorothricin (CHL), is presently unknown. gene clusters governing biosynthesis both contain a encoding an atypical member FkbH family enzymes, which has previously been shown synthesise glyceryl-S-acyl carrier protein (ACP) as first step in production extender units for modular biosynthesis. We show here that purified...
Say "when": Analysis of the biosynthetic gene cluster for polyether antibiotic and anticancer agent salinomycin (1) shows that its core structure is synthesised by a nine-multienzyme modular polyketide synthase. Deletion salC gene, which required oxidative cyclisation, has led to detection novel metabolite whose reveals timing key dehydration step. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or...
The identity and reactivity of the intermediates in agglomerin biosynthesis were established respective roles acetyltransferase Agg4 eliminating enzyme Agg5 identified (see scheme). It is proposed that enzymes homologous to carry out dehydration steps all spirotetronate biosynthetic pathways. If this proves correct, it may assist engineering these As a service our authors readers, journal provides supporting information supplied by authors. Such materials are peer reviewed be re-organized...
Abstract Endowing mesophilic microorganisms with high-temperature resistance is highly desirable for industrial microbial fermentation. Here, we report a cold-shock protein (CspL) that an RNA chaperone from lactate producing thermophile strain ( Bacillus coagulans 2–6), which able to recombinantly confer strong other microorganisms. Transgenic cspL expression massively enhanced growth of Escherichia coli (a 2.4-fold biomass increase at 45 °C) and eukaryote Saccharomyces cerevisiae 2.6-fold...
A novel mechanism is proposed for ring formation in the biosynthetic pathway to thiotetronate antibiotics thiolactomycin and Tü 3010.
Abstract Polyketides are a large family of pharmaceutically important natural products, and the structural modification their scaffolds is significant for drug development. Herein, we report high‐resolution X‐ray crystal structures broadly selective acyltransferase (AT) from splenocin polyketide synthase (SpnD‐AT) in apo form complex with benzylmalonyl pentynylmalonyl extender unit mimics. These revealed molecular basis stereoselectivity substrate specificity SpnD‐AT, enabled engineering...
Two new spirotetronate natural products, lobophorin L (1) and M (2), together with three known lobophorin-like antibiotics (3-5) two ansamycins (6-7), were isolated from the marine-derived Streptomyces sp. 4506. The structures of 1 2 established on basis HRESIMS as well 1D 2D NMR datasets. Antibacterial assay showed that, compounds 3-5 exhibited strong to moderate antibacterial activities against Micrococcus luteus Bacillus thuringiensis MIC values ranging 0.0625 8 μg/mL, while 3 6 weak...