A5066162156- Microbial Natural Products and Biosynthesis
- Phytochemical compounds biological activities
- Marine Sponges and Natural Products
- Genomics and Phylogenetic Studies
- Cancer therapeutics and mechanisms
- Chemical Synthesis and Analysis
- Plant biochemistry and biosynthesis
- Carbohydrate Chemistry and Synthesis
- Regulation of Appetite and Obesity
- Synthetic Organic Chemistry Methods
- Adipose Tissue and Metabolism
- Bioactive Compounds and Antitumor Agents
- Cyclization and Aryne Chemistry
- Microbial Metabolism and Applications
- RNA and protein synthesis mechanisms
- Fungal Biology and Applications
- Adipokines, Inflammation, and Metabolic Diseases
- DNA and Nucleic Acid Chemistry
- Peptidase Inhibition and Analysis
- Synthesis and Biological Evaluation
- Biochemical and Molecular Research
- Synthesis and Catalytic Reactions
- Plant Disease Resistance and Genetics
- Microbial Metabolic Engineering and Bioproduction
- Photochromic and Fluorescence Chemistry
University of Florida
2022-2024
Wuhan University
2024
Nanchang University
2024
Yonsei University
2016-2024
Yonsei University College of Dentistry
2018-2024
Guangxi University
2024
Guangxi Institute of Oceanography
2024
Ministry of Natural Resources
2024
Fourth People’s Hospital of Jinan
2023
Scripps Research Institute
2014-2023
Abstract With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role the discovery novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these are often organised into gene clusters (BGCs). In 2015, we defined Minimum Information about Biosynthetic Gene cluster (MIBiG): standardised format describes minimally required information to...
ABSTRACT The enediyne family of natural products has had a profound impact on modern chemistry, biology, and medicine, yet only 11 enediynes have been structurally characterized to date. Here we report genome survey 3,400 actinomycetes, identifying 81 strains that harbor genes encoding the polyketide synthase cassettes could be grouped into 28 distinct clades based phylogenetic analysis. Genome sequencing 31 representative confirmed each clade harbors biosynthetic gene cluster. A...
Significance Leinamycin (LNM) is a promising anticancer drug lead, yet no analog has been isolated since its discovery nearly 30 y ago. By mining bacterial genomes, we discovered 49 potential producers of LNM-type natural products, the structural diversity which was predicted based on bioinformatics and confirmed by in vitro characterization selected enzymes elucidation guangnanmycins weishanmycins. These findings demonstrate power discovery-based approach to combinatorial biosynthesis for...
Natural products offer unmatched chemical and structural diversity compared to other small-molecule libraries, but traditional natural product discovery programs are not sustainable, demanding too much time, effort, resources. Here we report a strain prioritization method for discovery. Central the is application of real-time PCR, targeting genes characteristic biosynthetic machinery with distinct scaffolds in high-throughput format. The practicality effectiveness were showcased by...
Abstract Aging is a recognized risk factor for periodontitis, while biological aging could provide more accurate insights into an individual's functional status. This study aimed to investigate the potential association between and periodontitis. Epidemiological data from 9803 participants in 2009–2014 National Health Nutrition Examination Survey were analyzed at cross-sectional level assess this link. Three ages [Klemera–Doubal method (KDM), PhenoAge, homeostatic dysregulation (HD)] two...
A new anthraquinone-fused enediyne, yangpumicin (YPM A, 1), along with four Bergman cyclization congeners B–E, 2–5), was isolated from Micromonospora yangpuensis DSM 45577 after mining enediyne biosynthetic gene clusters public actinobacterial genome databases and prioritizing the hits by an neighborhood network analysis for discovery. YPM is potent against a broad spectrum of human cancer cell lines. The discovery 1 provides opportunities functionalization enediynes to develop conjugation...
Dopaminergic (DA) neurons are involved in the integration of neuronal and hormonal signals to regulate food consumption energy balance. Forkhead transcriptional factor O1 (FoxO1) hypothalamus plays a crucial role mediation leptin insulin function. However, homoeostatic FoxO1 DA system has not been investigated. Here we report that is highly expressed mice lacking specifically (FoxO1 KODAT) show markedly increased expenditure interscapular brown adipose tissue (iBAT) thermogenesis accompanied...
The enediynes are structurally characterized by a 1,5-diyne-3-ene motif within 9- or 10-membered enediyne core. anthraquinone-fused (AFEs) subclass of that contain an anthraquinone moiety fused to the core as exemplified dynemicins and tiancimycins. A conserved iterative type I polyketide synthase (PKSE) is known initiate biosynthesis all cores, evidence has recently been reported suggest also originates from PKSE product. However, identity product converted not established. Here, we report...
Natural products remain the best sources of drugs and drug leads serve as outstanding small-molecule probes to dissect fundamental biological processes. A great challenge for natural product community is discover novel efficiently cost effectively. Here we report development a practical method survey biosynthetic potential in microorganisms, thereby identifying most promising strains prioritizing them discovery. Central our approach innovative preparation, by two-tiered PCR method, pool...
Significance The natural product leinamycin (LNM), upon reductive activation by cellular thiols, exerts its antitumor activity an episulfonium ion-mediated DNA alkylation. Manipulation of the LNM biosynthesis in Streptomyces atroolivaceus S-140 yielded a recombinant strain that produced biosynthetic intermediate, E1 (LNM E1). Complementary to can be oxidatively activated reactive oxygen species (ROS) generate similar ion thereby alkylating and leading eventual cell death. feasibility...
Angucyclines and angucyclinones are aromatic polyketides with a tetracyclic benz[a]anthracene skeleton. The scaffold is biosynthesized by type II polyketide synthases that catalyze the decarboxylative condensation of short acyl-CoA starter nine extender units. angucyclinones, largest group polycyclic polyketides, achieve structural diversity via subsequent oxidation, ring cleavage, amino acid incorporation, glycosylation. We here report discovery 14 two angucyclines (1-16) from Streptomyces...
Comparative analyses of the four known anthraquinone-fused enediynes biosynthetic gene clusters identified genes, tnmE6, tnmH, tnmL, and tnmQ, unique to tnm cluster. Larger scale fermentation both S. sp. CB03234 wild-type ΔtnmH ΔtnmL mutant strains resulted in characterization 20 new tiancimycin (TNM) congeners, including five enediynes. These findings enabled a proposal for late stage TNM biosynthesis featuring an intermediate possibly common all
Although activin receptor IIB (ACVR2B) is emerging as a novel pathogenic receptor, its ligand and assembled components (or assembly) are totally unknown in the context of osteoarthritis (OA) pathogenesis. The present results suggest that upregulation ACVR2B assembly could affect osteoarthritic cartilage destruction. It shown ligand, A, regulates catabolic factor expression through OA development. Activin A Tg mice (Col2a1-Inhba) exhibit enhanced destruction, whereas heterozygous KO (Inhba+/-...
The bleomycins (BLMs) are used clinically in combination with a number of other agents for the treatment several types tumors, and BLM, etoposide, cisplatin regimen cures 90-95% metastatic testicular cancer patients. BLM-induced pneumonitis is most feared, dose-limiting side effect BLM chemotherapy, which can progress into lung fibrosis affect up to 46% total patient population. There have been continued efforts develop new analogues search anticancer drugs better clinical efficacy lower...
Three natural products of nonaketide biosynthetic origin, probably biosynthesized from nine molecules malonyl-CoA, have been isolated. Herein we described the isolation and structure elucidation huanglongmycin (HLM) A-C identification putative hlm gene cluster Streptomyces sp. CB09001, isolated a karstic cave in Xiangxi, China. Albeit previously isolated, HLM A was reported for first time to exhibit moderate cytotoxicity against A549 lung cancer cell line (IC50 = 13.8 ± 1.5 μM) weak...
Abstract Development of metabolic syndrome is associated with hyperactivity the HPA axis characterized by elevated levels circulating adrenal hormones including cortisol and aldosterone. However, molecular mechanism leading to dysregulation not well elucidated. In this study, we found that insulin regulates steroidogenesis increasing expression activity steroidogenic factor 1 (SF-1) both in vitro vivo effect was partly through inhibition FoxO1. Specifically, increased protein RNA SF-1 target...