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MOLECULES · 2016 ·Vol. 21 ·期 8 ·970 · IF 2.465

Halichoblelide D, a New Elaiophylin Derivative with Potent Cytotoxic Activity from Mangrove-Derived Streptomyces sp. 219807

Ying Han,Erli Tian,Dongbo Xu,Min Ma,Zixin Deng,Kui Hong

During our search for interesting bioactive secondary metabolites from mangrove actinomycetes, the strainStreptomycessp. 219807 which produced a high elaiophylin yield of 4486 mg/L was obtained. A new elaiophylin derivative, halichoblelide D (1), along with seven known analogues2–8was isolated and identified from the culture broth. Their chemical structures were determined by detailed analysis of 1D and 2D NMR and HRMS data. The absolute configuration of halichoblelide D (1) was confirmed by comparing the CD spectrum with those of the reported analogues. Compounds1–7exhibited potent cytotoxic activities against HeLa and MCF-7 cells with IC50values ranging from 0.19 to 2.12 μM.Keywords:mangrove actinomycetes;Streptomycessp. 219807;elaiophylin;cytotoxic

研究领域: 微生物学 · 药物化学 · 肿瘤学
✓ 已验证 DOI PubMed 高影响因子
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NATURAL PRODUCT RESEARCH · 2024 · IF 1.9

Anti-vibriosis bioactive molecules from marine-derived variant Streptomyces sp. ZZ741A

Di Zhang,Yao Feng,Mingyi Chu,Yujiang Dai,Lu Jiang,Huifang Li

The infection of vibrio is an important cause of huge economic losses in aquaculture industry. At present, antibiotics are mainly used to prevent and reduce the infection of the vibrio, which has accelerated the emergence of multi-drug-resistant strains. New generation alternative anti-vibrio drugs were in urgent to solve this problem. In this study, six compounds (1–6) were isolated from the Streptomyces sp. ZZ741A, a marine-derived Streptomyces variant, including one new compound, 2-carbamoylphenyl isobutyrate (1), five known ones, nocardamine (2), dehydroxynocardamine (3), phenylacetic acid (4), thiophenol (5) and 2,3-dihydroxybenzoic acid (6). The anti-vibriosis assay showed that compounds 2 and 3 had specific inhibition activity against Vibrio vulnificus, Vibrio alginolyticus, and Vibrio parahaemolyticus with the MIC values ranging from 8 to 128 μg/mL. The molecular docking study of their possible mechanism of anti-vibriosis activity showed that the activity might come from the inhibition of Outer membrane protein U (OmpU).

CAS / MDL: 75-05-8 67-56-1
研究领域: 微生物学 · 水产养殖学 · 药理学
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APPLIED AND ENVIRONMENTAL MICROBIOLOGY · 2017 ·Vol. 83 ·期 15 · IF 3.807

Mathermycin, a Lantibiotic from the Marine Actinomycete Marinactinospora thermotolerans SCSIO 00652

Erquan Chen,Qi Chen,Shaoming Chen,Bing Xu,Jianhua Ju,Huan Wang

Lantibiotics are antimicrobial peptides belonging to the family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) and feature thioether linkages in their structures. In this study, we identified the biosynthetic gene cluster of a cinnamycin analog, named mathermycin, from Marinactinospora thermotolerans SCSIO 00652 and reconstituted its biosynthesis in Streptomyces lividans and Escherichia coli. Key posttranslational modification enzymes of mathermycin were characterized. Mathermycin exhibited antimicrobial activity and therefore represents an example of cinnamycin-like lantibiotics from Marinactinospora species.IMPORTANCE The discovery of new antimicrobial compounds that can be used as potential drugs is in urgent need due to increasing bacterial resistance to current antibiotics. Lantibiotics are important antimicrobial compounds that have found applications in both the clinic setting and food industry. We report here the discovery of a new lantibiotic, mathermycin, from a marine-derived Marinactinospora thermotolerans strain and elucidation of its biosynthesis. We also demonstrate that mathermycin possesses antimicrobial activity toward a Bacillus strain.

CAS / MDL: 50-81-7 7782-63-0
研究领域: 微生物学 · 药物化学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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AMB Express · 2021 ·Vol. 11 ·期 1 ·1-11 · IF 3.298

Antimicrobial compounds were isolated from the secondary metabolites of Gordonia, a resident of intestinal tract of Periplaneta americana

Ma Yan,Xu Minhua,Liu Hancong,Yu Tiantian,Guo Ping,Liu Wenbin,Jin Xiaobao

Gordonia sp. are members of the actinomycete family, their contribution to the environment improvement and environmental protection by their biological degradation ability, but there are few studies on the antimicrobial activity of their secondary metabolites. Our team isolated and purified an actinomycete WA 4-31 from the intestinal tract of Periplaneta americana, firstly identified the strain WA 4-31 by the morphological characteristics and the phylogenetic analyses, and found it was completely homologous to the strain of Gordonia terrae from the Indian desert. Meanwhile, actinomycin D (1), actinomycin X2 (2), mojavensin A (3) and cyclic (leucine-leucne) dipeptide (4) were obtained from the EtOAc extract from the broth of WA 4-31. Compounds 1–4 showed anti-fungus activities against Candida albicans, Aspergillus niger, A. fumigatus and Trichophyton rubrum, also anti-MRSA and inhibited Escherichia coli in different degree. Interestingly, we found when 3 was mixed with 4 with ratio of 1:1, the activity of the mixture on anti-Candida albicans was better than the single. Besides, compounds 1–3 had varying degrees of antiproliferative activities on CNE-2 and HepG-2 cell lines. These indicated that Gordonia rare actinomycete from the intestinal tract of Periplaneta americana possessed a potential as a source of active secondary metabolites.

研究领域: 微生物学 · 药理学 · 生物化学
✓ 已验证 DOI PubMed 高影响因子
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TRENDS IN BIOTECHNOLOGY · 2025 · IF 14.9

Tunable dynamic engineering of cellular NAD boosts the production of antibiotics in actinomycetes

Panpan Wu,Zhenyue Xu,Zhongqiu Meng,Ketao Chen,Hao Lin,Min Zhang,Lixin Zhang,Buchang Zhang,Hang Wu

Nicotinamide adenine dinucleotide (NAD) homeostasis is crucial for secondary metabolism in antibiotic-producing actinomycetes. However, NAD-based dynamic control strategies for boosting antibiotic titers have not been reported. We identified SACE_1905, an alcohol dehydrogenase in Saccharopolyspora erythraea , which converts NADH to NAD + . Overexpressing SACE_1905 lowered the cellular NADH/NAD + ratio, facilitating carbon source utilization and erythromycin biosynthetic precursor supply, concurrently improving cell growth and erythromycin yield. To balance primary and secondary metabolism, we developed a strategy that fine-tunes SACE_1905 expression with inducible clustered regularly interspaced short palindromic repeat interference (CRISPRi) to dynamically modulate the NADH/NAD + ratio, which we named diNAD. Optimized diNAD redirected carbon flux, maximizing erythromycin biosynthesis at a moderate NADH/NAD + ratio during the stationary phase. Based on its utility in actinorhodin and avermectin overproduction in Streptomyces coelicolor and Streptomyces avermitilis , we show that diNAD is effective in augmenting antibiotic titers in actinomycetes.

研究领域: 微生物学 · 生物技术 · 合成生物学 · 生物工程 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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LWT-FOOD SCIENCE AND TECHNOLOGY · 2022 · IF 6.056

Heterologous expression and characterization of amine oxidases from Saccharopolyspora to reduce biogenic amines in huangjiu

Shuangping Liu,Hongli Yao,Mengfei Sun,Zhilei Zhou,Jian Mao

High content of biogenic amines in fermented food has adverse effects on the human body. Previous studies showed that biogenic amines could be reduced in some fermented foods using enzymes. However, this process was barely explored in alcoholic beverages. In this study, potential biogenic amine degarding genes were cloned from Saccharopolyspora hirsuta F1902 and Saccharopolyspora hordei F2002, and expressed in E. coli to study the enzymatic activities of copper-containing amine oxidases named as CaoA Shi and CaoA Sho in huangjiu . The degradation ratio of total biogenic amines by CaoA Shi (31.72%) was higher than that of CaoA Sho (24.37%). CaoA Shi and CaoA Sho had the highest degradation ratios of histamine, phenylethylamine, followed by tyramine, tryptamine or putrescine, and the smallest was cadaverine. The results indicated that CaoA Shi had better biodegradability of biogenic amines than CaoA Sho in huangjiu (P < 0.05), and the two enzymes had the same amine substrate characteristics. These results provide new insights for the reduction of biogenic amines using amine oxidases, which is useful not only for huangjiu brewing industry, but also for other fermented food industries.

研究领域: 食品科学 · 微生物学 · 酶学 · 饮料技术
✓ 已验证 DOI 高影响因子
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Fermentation-Basel · 2023 ·Vol. 9 ·期 4 ·398 · IF 3.7

Enhanced Pentostatin Production in Actinomadura sp. by Combining ARTP Mutagenesis, Ribosome Engineering and Subsequent Fermentation Optimization

Hongyu Zhang,Deguang Zhang,Ran Liu,Tingting Lou,Ruyue Tan,Suying Wang

The special structure of pentostatin causes it to possess a wide spectrum of biological and pharmacological properties, and it has been extensively employed to treat malignant tumors and is the first-line treatment for hairy cell leukemia. Pentostatin is mainly distributed in several actinomycetes and fungi species. However, its low titer in microbes is not able to meet medical needs. Here, we report a strain improvement strategy based on combined atmospheric and room-temperature plasma (ARTP) mutagenesis and ribosome engineering screening, as well as fermentation optimization, for enhanced pentostatin production. The original strain,Actinomadurasp. ATCC 39365, was treated with ARTP and screened by ribosome engineering to obtain one stable pentostatin high-yield mutantActinomadurasp. S-15, which produced 86.35 mg/L pentostatin, representing a 33.79% increase compared toActinomadurasp. ATCC 39365. qRT-PCR analysis revealed that pentostatin biosynthesis-related gene expression was significantly upregulated inActinomadurasp. S-15. Then, to further enhance pentostatin production, the fermentation medium was optimized in flask culture and the pentostatin production ofActinomadurasp. S-15 reached 152.06 mg/L, which is the highest pentostatin production reported so far. These results demonstrate the effectiveness of combined ARTP mutation, ribosome engineering screening, and medium optimization for the enhancement of pentostatin production, and provide a methodology enabling the sustainable production of pentostatin on an industrial scale.Keywords:Actinomadurasp.;pentostatin;atmospheric and room temperature plasma;ribosome engineering

CAS / MDL: 53910-25-1
研究领域: 微生物学 · 生物技术 · 药理学
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STAR Protocols · 2023 · IF 0

An in vitro CRISPR-Cas12a-mediated protocol for direct cloning of large DNA fragments

Xiaoqian Zeng,Shuliu Wang,Mindong Liang,Weishan Wang,Yue Jiang,Fei Xu,Leshi Liu,Hao Yan,Yaojun Tong,Lixin Zhang,Gao-Yi Tan

Summary Large biosynthetic gene cluster (BGC) cloning is important for discovering natural product-based drugs and remains challenging in high GC content microorganisms (e.g., Actinobacteria). Here, we present an in vitro CRISPR-Cas12a-mediated protocol for direct cloning of large DNA fragments. We describe steps for crRNA design and preparation, genomic DNA isolation, and CRISPR-Cas12a cleavage and capture plasmid construction and linearization. We then detail target BGC and plasmid DNA ligation and transformation and screening for positive clones. For complete details on the use and execution of this protocol, please refer to Liang et al. 1

研究领域: 分子生物学 · 生物技术 · 基因工程
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Colloid and Interface Science Communications · 2018 · IF 0

From Homogeneous to Heterogeneous: A Simple Approach to Prepare Polymer Brush Modified Surfaces for Anti-Adhesion of Bacteria

Xiao-Hong Zhang,Hai-Xia Wu,Lin Huang,Chuan-Jun Liu

In this paper, the hydrophilic p( N -hydroxyethylacrylamide) (PHEAA) brush was grafted from silicon wafer, followed by the decoration of C 3 F 7 groups with low surface energy to the side chains of PHEAA brush. The anti-adhesion performance of the modified surfaces was evaluated using Actinomyces naeslundii and Streptococcus mutans . For 4 h incubation, the silicon wafer with PHEAA brush (Si-PHEAA) was able to resist the adhesion of bacteria, while the anti-adhesion of the PHEAA-C 3 F 7 decorated silicon wafer (Si-PHEAA-C 3 F 7 ) had been improved. When the incubation time was extended to 24 h, the Si-PHEAA-C 3 F 7 still exhibited excellent adhesion-repellent property against bacteria. And among the Si-PHEAA-C 3 F 7 surfaces with 2.6%, 9% and 13% grafting degrees of C 3 F 7 , there was no obvious difference in anti-adhesion performance. The results indicated that the method of polymerization prior to decoration is easy to operate, moreover the prepared Si-PHEAA-C 3 F 7 possessed the long-term and high-efficiency anti-adhesion of bacteria ability.

研究领域: 材料科学 · 生物材料 · 表面化学 · 微生物学
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Synthetic and Systems Biotechnology · 2019 · IF 0

Efficient editing DNA regions with high sequence identity in actinomycetal genomes by a CRISPR-Cas9 system

Jingjun Mo,Shuwen Wang,Wan Zhang,Chunyu Li,Zixin Deng,Lixin Zhang,Xudong Qu

Actinobacteria able to produce varieties of bioactive natural products have been long appreciated by the field of drug discovery and development. Recently, a few of CRISPR/Cas9 systems bearing different types of replicons (pSG5 and pIJ101) were developed to efficiently edit their genomes. Despite wide application in gene editing, their utility in editing challenging DNA regions e.g. high sequence identity has not been compared. In this study, we confirmed that the widely used temperature-sensitive pSG5 replicon is indeed not suitable for editing modular polyketide synthase (PKS) genes due to causing unpredicted gene recombination. This problem can be addressed by replacing the pSG5 with the segregationally unstable pIJ101 replicon. By introducing a counter-selection marker CodA, convenient cloning sites in the single guide RNAs (sgRNAs) and homologous template scaffolds, we developed a new CRISPR-Cas9 system pMWCas9. This system was successfully used to delete/replace erythromycin PKS and other biosynthetic genes in Saccharopolyspora erythraea and Streptomyces sp. AL2110. By swapping the promoters of antB and antC with ermE and kasOp , we achieved a deacyl-antimycin hyper producer which produces a 9-fold higher yield than the original Streptomyces sp. AL2110 strain. Our results provide a robust and useful Cas9 tool for genetic studies in Actinobacteria .

研究领域: 遗传学 · 微生物学 · 生物技术 · 药物发现
✓ 已验证 DOI PubMed
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FOOD HYDROCOLLOIDS · 2023 · IF 10.7

In vitro digestion and fecal fermentation of encapsulated starch constructed via layer-by-layer coating of calcium alginate

Congli Cui,Mingju Li,Xiaoyang He,Na Ji,Yang Qin,Lei Dai,Liu Xiong,Qingjie Sun

This research prepared functional-resistant starch capsules by constructing multiple calcium alginate shells around calcium alginate/starch beads. Scanning electron microscopy revealed a dense structure for each layer of the calcium alginate shell, tightly encapsulating the calcium alginate/starch beads. The rapidly digestive starch content of three-layer calcium alginate shelled starch capsules decreased to 0.50 ± 1.14%, while the resistant starch content increased to 78.25 ± 1.55%. The estimated glycemic index (eGI) experiment suggested that the two-layer shell capsules (eGI: 59.91) and Three-layer shell capsules (eGI: 47.75) were classified as low-glycemic index foods . Furthermore, calcium alginate/corn starch multilayer capsules showed reduced microbial gas production and increased concentrations of propionic acid , isobutyric acid, and valeric acid compared to lactulose in vitro fecal fermentation experiment. Moreover, three-layer capsules and beads promoted a relative abundance of Bacteroidetes but inhibited the reproduction of Proteobacteria and Actinobacteria compared with lactulose and corn starch. These results suggest that constructing multi-layered sodium alginate shells for starch beads can effectively increase the digestive resistance of starch within the capsules and control its fermentation in the colon. This study will have a profound impact on the development of RS1-type resistant starch and be beneficial in the design and production of functional foods for prevention and assistance in the treatment of chronic diseases such as diabetes and obesity.

CAS / MDL: 3326-32-7
研究领域: 食品科学 · 营养学 · 微生物学 · 生物技术
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ENVIRONMENTAL POLLUTION · 2022 · IF 9.988

Combined effects of spent mushroom substrate and dicyandiamide on carbendazim dissipation in soils: Double-edged sword effects and potential risk controls

Andong Wang,Dongsheng Zou,Zhihong Xu,Bin Chen,Xiaopeng Zhang,Falin Chen,Manyun Zhang

Repeated and high-dose carbendazim applications have caused serious soil carbendazim contamination, and eco-friendly and economical approaches have been suggested to promote carbendazim removal in agricultural soil . Spent mushroom substrate (SMS) is a special recycled resource after harvesting mushrooms and can be utilized in contaminated soil amendment. The SMS application into agricultural soil might increase antibiotic resistance gene abundances, and the health risks of SMS application might be reduced with reasonable management to adjust the related electron transport of soil nitrification or denitrification. In this study, the SMS and nitrification inhibitor dicyandiamide were used to remediate agricultural soil contaminated with the carbendazim, and the carbendazim contents, soil microbial biomass, activities and community and human disease genes were determined. Compared to the control treatment, the combined applications of SMS and dicyandiamide significantly decreased soil carbendazim content by 38.14% but significantly enhanced soil β -glucosidase, chitinase, arylsulfatase, urease and electron transfer system activities. The relative abundances of Proteobacteria and Actinobacteria were increased by 11.0% and 8.2% with the SMS application, respectively. The carbendazim residues were negatively correlated with the soil pH, electron transfer system activities and relative abundances of Proteobacteria and Actinobacteria. The relative abundances of human disease genes were also dramatically increased with the SMS application, but compared to the SMS alone, extra dicyandiamide application significantly reduced the relative abundances of human disease genes in soils. The SMS applications into fungicide-contaminated soils could generate double-edged sword effects of facilitating fungicide dissipation but leading to potential health risk increase, while applying the dicyandiamide with SMS might be an effective strategy to decrease the negative effect of health risk.

CAS / MDL: 10605-21-7
研究领域: 环境科学 · 土壤学 · 微生物学 · 生态毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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