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1.
Chem Biodivers ; 21(5): e202400090, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38486477

RESUMEN

Streptomide (1), a new amide analogue, streptomynone (2), a new quinolinone, and ten known compounds including three aliphatic acids (3-5), two amides (6-7), four cyclic dipeptides (8-11), and an adenosine (12) were isolated from the fermentation broth of Streptomyces sp. YIM S01983 isolated from a sediment sample collected in Bendong Village, Huadong Town, Chuxiong, China. Their structures were determined by analysis of the 1D/2D-NMR and HR-ESI-MS spectra. Compound 12 presented weak antimicrobial activities against Candida albicans and Aligenes faecalis (MIC=64 µg/mL). Compounds 7 and 12 showed weak cytotoxic activity against MHCC97H.


Asunto(s)
Amidas , Candida albicans , Pruebas de Sensibilidad Microbiana , Quinolonas , Streptomyces , Streptomyces/química , Streptomyces/metabolismo , Amidas/química , Amidas/farmacología , Amidas/aislamiento & purificación , Candida albicans/efectos de los fármacos , Quinolonas/química , Quinolonas/farmacología , Quinolonas/aislamiento & purificación , Humanos , Línea Celular Tumoral , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Enterococcus faecalis/efectos de los fármacos , Estructura Molecular , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales
2.
Ecotoxicol Environ Saf ; 256: 114840, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37001191

RESUMEN

Harmful cyanobacterial blooms have caused numerous biosecurity incidents owing to the production of hazardous secondary metabolites such as microcystin. Additionally, cyanobacteria also release many other components that have not been explored. We identified compounds of a toxic mixture exudated from a dominant, blooming species, Microcystis aeruginosa, and found that phytosphingosine (PHS) was one of the bioactive components. Since PHS exhibited toxicity and is deemed a hazardous substance by the European Chemicals Agency, we hypothesized that PHS is a potentially toxic compound in M. aeruginosa exudates. However, the mechanisms of PHS ecotoxicity remain unclear. We assessed the cytotoxicity of PHS using an in vitro cell model in eight human cell lines and observed that the nasopharyngeal carcinoma cell line CNE2 was the most sensitive. We exposed CNE2 cells to 0-25 µmol/L PHS for 24 hr to explore its toxicity and mechanism. PHS exposure resulted in abnormal nuclear morphology, micronuclei, and DNA damage. Moreover, PHS significantly inhibited cell proliferation and arrested cell cycle at S phase. The results of Western blot suggested that PHS increased the expression of DNA damage-related proteins (ATM, p-P53 and P21) and decreased the expression of S phase-related proteins (CDK2, CyclinA2 and CyclinE1), indicating the toxicological mechanism of PHS on CNE2 cells. These data provide evidence that PHS has genetic toxicity and inhibits cell proliferation by damaging DNA. Our study provides evidence that PHS inhibits cell proliferation by damaging DNA. While additional work is required, we propose that PHS been considered as a potentially toxic component in MaE in addition to other well-characterized secondary compounds.


Asunto(s)
Cianobacterias , Microcystis , Humanos , Microcistinas/toxicidad , Proliferación Celular , Línea Celular
3.
Chem Biodivers ; 20(3): e202201240, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36799244

RESUMEN

Jiangchuanmycin (1), a new indole containing pyrrolizidine, and six known peptides (2-7) were obtained from the fermentation broth of a Streptomyces isolate collected from a sediment sample of Xingyun Lake, Jiangchuan, China. Their structures were elucidated on the detailed analysis of the HR-ESI-MS, 1D and 2D NMR, ECD, and X-ray crystallographic data. Jiangchuanmycin (1) presented weak inhibitory effects on cell lines of H1299, MHCC97H, HCT116 with the IC50 values of 97.6 µM, 98.6 µM and 40.6 µM, respectively.


Asunto(s)
Antineoplásicos , Streptomyces , Streptomyces/química , Estructura Molecular , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Espectroscopía de Resonancia Magnética
4.
Sensors (Basel) ; 23(9)2023 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-37177391

RESUMEN

With the development of infrared detection and imaging technology, infrared cameras (IRCs) play an important role in many fields, such as military, industry, and civilian. Additionally, the requirements for the size, performance, and intelligence of IRCs are becoming more and more strict. Consequently, the associated research and development (R&D) of IRCs is gradually focused on the aspects of miniaturization, high performance, intelligence, low power consumption, and low cost, involving many frontier fields, including artificial intelligence, new materials, new optical systems, and electronics systems. In fact, there are continual studies on intelligent SWaP3 IRCs, but unfortunately, a systematic arrangement and analysis are lacking. Therefore, a systematical and comprehensive review for the developments and core technologies of the intelligent SWaP3 IRCs is really needed. In this paper, in terms of the aforementioned requirements, we conduct a review and analysis of current intelligent SWaP3 IRCs based on 90 literature and statistics in recent decades to provide the relevant developers with a helpful reference for facilitating the indicator optimization of intelligent SWaP3 IRCs with new developed technologies. We analyze the development of SWaP3 IRCs in the aspects of lightweight, miniaturization, low price, and high performance, including hyperspectral resolution, high spatial resolution, large field of view (FOV), and wide dynamic elaborately. Moreover, the development in low power consumption and intelligence is also discussed in detail. Additionally, we briefly summarize the primary applications of intelligent SWaP3 IRCs in military, scientific, and civil. Then, the core technologies comprising high-integration, lightweight, hyperspectral imaging (HSI), low-power consumption, as well as the realization of high performance such as high-resolution, high-frame, and wide-dynamic range of SWaP3 IRCs are discussed and analyzed in detail. Finally, we prospect for the intelligent SWaP3 IRCs that it is necessary to continuously expand the concept of SWaP3 by reliability, stability, extensibility, and safety. In addition, it is useful to embed cutting-edge technologies such as small pixel pitch array, multi-sensors fusion, and deploy intelligent algorithms to IRCs. Additionally, the improvement of the whole machine from multi-dimension such as chip, camera, and system is expected and needs to be taken more seriously. It is hoped that this paper can provide a reference for the R&D of intelligent SWaP3 IRCs in the future.

5.
Angew Chem Int Ed Engl ; 62(32): e202304434, 2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37340694

RESUMEN

Activation of nitromethane to endow new reactivity is an interesting and meaningful but also challenging topic. Herein, we report an electrochemical activation of nitromethane to serve as both the heterocyclic skeleton and oxime sources for the construction of isoxazoline aldoximes. The isoxazoline aldoximes that are prepared by four steps with the reported strategy are synthesized in a single step from low-cost and readily available nitromethane and olefins with moderate to excellent yields under our electrochemical conditions. The reaction also takes advantage of high atom-economy and E-selectivity. Moreover, the mechanism is studied by control experiments, a kinetic isotope effect (KIE) study, cyclic voltammogram (CV) experiments, and density functional theory (DFT) calculations. The mechanistic results reveal that nitromethane may be activated under electrochemical conditions to deliver a 1,2,5-oxadiazole 2-oxide intermediate, which undergoes [3+2] cycloaddition with olefins to yield isoxazoline aldoximes.

6.
Chem Biodivers ; 19(5): e202200064, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35333437

RESUMEN

Actinomycetes have being regarded as a treasure reservoir of various bioactive secondary metabolites and devoted many antibiotics in clinicals. Amycolatopsis sp. YNNP 00208 was isolated from a soil sample collected in Gaoligong Mountain area, Yunnan Province, China. Chemical investigation of its fermentation broth led to a new amide, baoshanmycin (1), and a new furanone derivative, 3-(1,3-dihydroxybutyl)-4-methylfuran-2(H)-one (2), together with eight known compounds, including two amides (3-4), four cyclic dipeptides (5-8), and two deoxyribonucleosides (9-10). Their structures were established on basis of the 1D- and 2D-NMR spectroscopic data, along with the HR-ESI-MS experiments. Baoshanmycin (1) showed moderate antimicrobial activities against Candida albicans, and weak activities against Staphylococcus aureus, multi-drug resistant Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes, fluconazole-resistant Candida albicans. Baoshanmycin (1) presented strong antioxidant activity and moderate anti-acetylcholinesterase activity. The other compound 3-(1,3-dihydroxybutyl)-4-methylfuran-2(H)-one (2) and the known compounds (3-10) showed moderate antioxidant activity.


Asunto(s)
Actinobacteria , Staphylococcus aureus Resistente a Meticilina , Actinobacteria/metabolismo , Amycolatopsis , Antibacterianos/química , Antioxidantes/metabolismo , China , Staphylococcus aureus Resistente a Meticilina/metabolismo , Pruebas de Sensibilidad Microbiana , Suelo
7.
Am J Orthod Dentofacial Orthop ; 162(4): e192-e202, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35987884

RESUMEN

INTRODUCTION: The phenomenon of orthodontic anchorage miniscrews loosening after being implanted several times happens in daily clinical practice, and the reasons need to be traced. This study aimed to investigate the underlying risk factors influencing the progressive susceptibility of orthodontic miniscrews to failure. METHODS: Overall, 889 miniscrews were successively inserted into 347 patients because some loosened or fell off once, twice, or more before achieving their purposes. The number of miniscrew failures (ie, once, twice, or more) was defined as progressive susceptibility to failure. The clinical indicators were assessed via univariate analysis, multicollinearity diagnosis, and Poisson log-linear regression model with stepwise calculation to screen out. RESULTS: The progressive susceptibility of miniscrews to failure was proved to be affected by the age of patients, the onset of force application, site of placement, and appliance type. Age and onset of force application presented a negative relationship with susceptibility. Miniscrews inserted in the palatal region appeared to be more stable than the forepart of the arch. In contrast, the retromaxillary and retromandibular areas obtained the lowest stability. The patients with fixed appliances were more unlikely to suffer progressive failure than removable appliances. In addition, the larger number of screws inserted in each patient, the greater probability of failure. CONCLUSIONS: Younger people with removable appliances that miniscrews inserted in the retromaxillary or retromandibular regions and earlier onsets of loading had a higher progressive susceptibility to loosening. Meanwhile, the failure rate was elevated with the increasing number of screws per patient received.


Asunto(s)
Métodos de Anclaje en Ortodoncia , Tornillos Óseos , Humanos , Métodos de Anclaje en Ortodoncia/efectos adversos , Diseño de Aparato Ortodóncico , Hueso Paladar/cirugía , Factores de Riesgo
8.
Am J Orthod Dentofacial Orthop ; 161(1): e12-e19, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34376339

RESUMEN

INTRODUCTION: This retrospective study aimed to quantify the impact of coronavirus disease 2019 (COVID-19) on the orthodontic appointment and make an analysis of orthodontic emergencies (OEs) that occurred during the pandemic. METHODS: A total of 628 patients were randomly sampled from 3489 subjects who were undergoing active orthodontic treatment with fixed appliances, and the medical records were reviewed. OE occurrence was analyzed from 617 patients who had explicit return-visit records after the COVID-19 outbreak. Wilcoxon signed rank tests, chi-square tests, and a binary logistic regression were performed. RESULTS: The return-visit of 98.6% of the patients was delayed significantly with an increase over 8.98 ± 4.76 weeks (P <0.001). In general, 32.3% of the patients suffered from various OEs while waiting for their first return-visit, and bracket or band debonding was the most frequently reported category. Most OEs did not receive timely treatments because of the lockdown. The incidence was nearly 2 times higher than that of the normal appointment times. No correlation was found between OE occurrence and different demographic and clinical characteristics of patients. The therapeutic progress of patients, especially those in stage 3, was postponed because of the occurrence of OEs. CONCLUSIONS: Regardless of the limitations, our study suggested that it is highly possible that the COVID-19 pandemic has delayed appointments of fixed orthodontic patients. OEs did bother a minority of patients and could not be settled in time during the lockdown, which had a negative impact on the near-term treatment progress and should have been prevented. Further studies are required to investigate the long-dated influence of COVID-19 on orthodontic practices.


Asunto(s)
COVID-19 , Control de Enfermedades Transmisibles , Humanos , Pandemias , Estudios Retrospectivos , SARS-CoV-2
9.
J Am Chem Soc ; 143(3): 1618-1629, 2021 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-33412858

RESUMEN

Transition metal catalysis that utilizes N-heterocyclic carbenes as noninnocent ligands in promoting transformations has not been well studied. We report here a cyclic (alkyl)(amino)carbene (CAAC) ligand-promoted nitro deoxygenative hydroboration with cost-effective chromium catalysis. Using 1 mol % of CAAC-Cr precatalyst, the addition of HBpin to nitro scaffolds leads to deoxygenation, allowing for the retention of various reducible functionalities and the compatibility of sensitive groups toward hydroboration, thereby providing a mild, chemoselective, and facile strategy to form anilines, as well as heteroaryl and aliphatic amine derivatives, with broad scope and particularly high turnover numbers (up to 1.8 × 106). Mechanistic studies, based on theoretical calculations, indicate that the CAAC ligand plays an important role in promoting polarity reversal of hydride of HBpin; it serves as an H-shuttle to facilitate deoxygenative hydroboration. The preparation of several commercially available pharmaceuticals by means of this strategy highlights its potential application in medicinal chemistry.

10.
Appl Environ Microbiol ; 87(19): e0106621, 2021 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-34505824

RESUMEN

Amycolatopsis sp. strain TNS106 harbors a ristomycin-biosynthetic gene cluster (asr) in its genome and produces ristomycin A. Deletion of the sole cluster-situated StrR family regulatory gene, asrR, abolished ristomycin A production and the transcription of the asr genes orf5 to orf39. The ristomycin A fermentation titer in Amycolatopsis sp. strain TNS106 was dramatically improved by overexpression of asrR and a heterologous StrR family regulatory gene, bbr, from the balhimycin-biosynthetic gene cluster (BGC) utilizing strong promoters and multiple gene copies. Ristomycin A production was improved by approximately 60-fold, resulting in a fermentation titer of 4.01 g/liter in flask culture, in one of the engineered strains. Overexpression of AsrR and Bbr upregulated transcription of tested asr biosynthetic genes, indicating that these asr genes were positively regulated by AsrR and Bbr. However, only the promoter region of the asrR operon and the intergenic region upstream of orf12 were bound by AsrR and Bbr in gel retardation assays, suggesting that AsrR and Bbr directly regulated the asrR operon and probably orf12 to orf14 but no other asr biosynthetic genes. Further assays with synthetic short probes showed that AsrR and Bbr specifically bound not only probes containing the canonical inverted repeats but also a probe with only one 7-bp element of the inverted repeats in its native context. AsrR and Bbr have an N-terminal ParB-like domain and a central winged helix-turn-helix DNA-binding domain. Site-directed mutations indicated that the N-terminal ParB-like domain was involved in activation of ristomycin A biosynthesis and did not affect the DNA-binding activity of AsrR and Bbr. IMPORTANCE This study showed that overexpression of either a native StrR family regulator (AsrR) or a heterologous StrR family regulator (Bbr) dramatically improved ristomycin A production by increasing the transcription of biosynthetic genes directly or indirectly. The conserved ParB-like domain of AsrR and Bbr was demonstrated to be involved in the regulation of asr BGC expression. These findings provide new insights into the mechanism of StrR family regulators in the regulation of glycopeptide antibiotic biosynthesis. Furthermore, the regulator overexpression plasmids constructed in this study could serve as valuable tools for strain improvement and genome mining for new glycopeptide antibiotics. In addition, ristomycin A is a type III glycopeptide antibiotic clinically used as a diagnostic reagent due to its side effects. The overproduction strains engineered in this study are ideal materials for industrial production of ristomycin A.


Asunto(s)
Amycolatopsis/genética , Amycolatopsis/metabolismo , Hemaglutininas/biosíntesis , Ristocetina/biosíntesis , Fermentación , Genes Bacterianos , Genes Reguladores , Ingeniería Metabólica , Familia de Multigenes
11.
Bioorg Med Chem ; 29: 115849, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33221063

RESUMEN

Neothalfine is a natural bisbenzylisoquinoline alkaloid with the abundant resource in medicinal plants and has not been reported its anti-tumor efficacy. In the present study, the anti-tumor efficacy was investigated and it showed broad-spectrum activity against several cancer cell lines, especially metastatic colorectal cancer (HCT116, SW620, T84) with the IC50 values of 7.2, 5.9, 8.2 nM, respectively, roughly equal to well-known anti-tumor agent docetaxel (4.0, 4.7, 2.7 nM) and nearly 1000 folds than CPT-11 (4.4, 5.1, 6.9 µM). Furthermore, neothalfine inhibited colorectal cell proliferation by resulting in cell cycle arrest at the G2/M phase and induced apoptosis through the dysfunction of mitochondria to trigger intrinsic apoptotic pathway by untargeted metabolomic method, mitochondrial membrane potential, and caspase-3/7 activity assay. Moreover, neothalfine damaged colorectal cancer clonal spheres expansion significantly at the concentration of 3.5 nM with nearly 1000 folds efficacy than CPT-11 (3.0 µM). The results supported that neothalfine might be an anti-tumor lead for further investigation.


Asunto(s)
Antineoplásicos/farmacología , Productos Biológicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Antineoplásicos/química , Productos Biológicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/secundario , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estructura Molecular , Relación Estructura-Actividad
12.
Chem Biodivers ; 18(9): e2100460, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34369658

RESUMEN

A new compound named koninginin W (1) and four known polyketides (2-5) were isolated from endophytic fungus Trichoderma koningiopsis YIM PH30002 of Panax notoginseng. The structures of 1 - 5, including absolute configuration of 1, were elucidated on the detailed analysis of the HR-ESI-MS, 1D and 2D NMR, and X-ray crystallographic data. Koninginin W (1) presented weak antibacterial activity against Escherichia coli, Bacillus subtilis and Salmonella typhimurium.


Asunto(s)
Antibacterianos/farmacología , Bacillus subtilis/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Salmonella typhimurium/efectos de los fármacos , Trichoderma/química , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Conformación Molecular
13.
Chem Biodivers ; 18(3): e2000964, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33533151

RESUMEN

Endophytic fungi play important roles for host's stress tolerance including invasion by pathogenic microbes. Small molecules are common weapons in the microbe-microbe interactions. Panax notoginseng is a widely used traditional Chinese medicinal plant and harbors many endophytes, some exert functions against pathogens. Here, we report six new compounds named myrothins A-F (1-6) produced by Myrothecium sp. BS-31, an endophyte isolated from P. notoginseng, and their antifungal activities against pathogenic fungi causing host root-rot disease. Their structures were elucidated with analysis of spectroscopic data including 1D and 2D NMR, HR-ESI-MS. Myrothins B (2) and E (5) showed the weak activity against Fusarium oxysporum and Phoma herbarum, and myrothins F (6) showed weak activity against F. oxysporum.


Asunto(s)
Antifúngicos/farmacología , Endófitos/química , Hypocreales/química , Panax notoginseng/microbiología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Fusarium/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Phoma/efectos de los fármacos , Estereoisomerismo , Relación Estructura-Actividad
14.
Phytochem Anal ; 32(5): 749-756, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33331092

RESUMEN

INTRODUCTION: The structural annotation of target relies on high-resolution mass spectrometry (HRMS) information resulting in dubious identities in most cases. The accurate annotation of isomeric structures is still challenging to be confirmed with significant bottleneck. OBJECTIVE: This study focused on the improvement of structural annotation of candidate structures via four pairs of isomeric flavanone-7-O-diglucosides and their basic flavanone aglycones commonly detected in citrus products. METHOD: An integrated liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) approach merging retention time, accurate mass, tandem mass spectrometry (MS/MS) information (diagnostic ions), ion ratio at selected collision energy was established successfully. RESULTS: Feasibility of this approach was validated confidently in biological samples with relative standard deviation (RSD) of ion ratio range from 3.91 to 12.28%. Differences of fragmentation patterns of citrus flavanones were illustrated reasonably. MS/MS fragments of (S)-hesperetin and (S)-isosakuranetin were complicated and showed typical radical ion [1,2 A - H]•- (m/z 164) in negative ESI mode due to the methoxyl group on B-ring, which showed huge difference with (R)-hesperetin and (R)-isosakuranetin. CONCLUSION: This study integrated multiple levels to boost the confidence of structural annotation relied on LC-HRMS, and provided important values in practice for precise identification of citrus flavanones in biological matrices.


Asunto(s)
Citrus , Flavanonas , Cromatografía Liquida , Flavanonas/análisis , Humanos , Isomerismo , Espectrometría de Masas en Tándem
15.
Indian J Microbiol ; 61(4): 519-523, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34744207

RESUMEN

Ten compounds (1-10) were obtained from soil-derived Penicillium cremeogriseum W1-1 with the antimicrobial guided isolation procedure. Among them, 4 presented broad-spectrum antimicrobial activities and its preliminary mechanisms were evaluated. Compound 4 showed growth inhibition on drug-resistant pathogenic strains Escherichia coli and Candida albicans with post-contact effect (PCE), changed the morphology and membrane structure, killed cells with leakage, inhibited the growth of C. albicans by eradicating biofilms. Interestingly, the fraction containing 4 presented in vivo anti-pathogenic activities in mice, indicating this indole diterpenoid alkaloid could been used as potential antimicrobial agent.

16.
J Am Chem Soc ; 142(29): 12834-12840, 2020 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-32589414

RESUMEN

Reductive cross-coupling between two chemically inert bonds remains a great challenge in synthetic chemistry. We report here the reductive cross-coupling between unactivated C(aryl)-N and C(aryl)-O bonds that was achieved by chromium catalysis. The simple and inexpensive CrCl2 salt, combined with important bipyridyl ligand and magnesium reductant, shows high reactivity in the successive cleavage of C(aryl)-N bonds of aniline derivatives and C(aryl)-O bonds of aryl esters, allowing the cross-coupling of these two unactivated and different bonds to occur in a reductive fashion to form a C(aryl)-C(aryl) bond. Mechanistic studies by deuterium-labeling experiments indicate that the C(aryl)-N bonds in anilines are preferentially cleaved by reactive Cr species, in which the ligation of bipyridyl with Cr by adopting a coordination model in 1:1 ratio can be considered.

17.
Antonie Van Leeuwenhoek ; 113(2): 165-174, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31552514

RESUMEN

Strain YIM PH21724T was isolated from the rhizosphere of Panax notoginseng. Phylogenetic analyses based on 16S rRNA gene sequences showed that the strain exhibits close phylogenetic relatedness to Nocardia kroppenstedtii N1286T (97.70%), Nocardia farcinica NCTC 11134T (97.67%) and Nocardia puris DSM 44599T (97.40%). The menaquinones were identified as MK-9 (H4), MK-8 (H4, ω-cyclo) and MK-8 (H4), and the major fatty acids (> 10%) were identified as C16:0, C18:1 ω9c and C18:0 10-methyl. The polar lipids were found to be composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides and an unidentified lipid. The G + C content of the genomic DNA was determined to be 67.01 mol%. The phenotypic, chemotaxonomic, phylogenetic and genomic results clearly show strain YIM PH21724T should be classified in the genus Nocardia and represents a novel species, for which the name Nocardia panacis sp. nov. is proposed. The type strain is YIM PH21724T (= DSM 105904T = KCTC 49030T = CCTCC AA 2017043T).


Asunto(s)
Actinobacteria/efectos de los fármacos , Panax notoginseng/química , Extractos Vegetales/farmacología , Rizosfera , Composición de Base/genética , Composición de Base/fisiología , Cardiolipinas/metabolismo , ADN Bacteriano/metabolismo , Nocardia , Fosfatidiletanolaminas/metabolismo , Fosfatidilinositoles/metabolismo , Filogenia , Extractos Vegetales/química , ARN Ribosómico 16S/metabolismo , Microbiología del Suelo , Vitamina K 2/metabolismo
18.
Proc Natl Acad Sci U S A ; 114(52): E11131-E11140, 2017 12 26.
Artículo en Inglés | MEDLINE | ID: mdl-29229819

RESUMEN

Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm-type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.


Asunto(s)
Actinobacteria , Proteínas Bacterianas , Genes Bacterianos/fisiología , Lactamas/metabolismo , Macrólidos/metabolismo , Familia de Multigenes/fisiología , Filogenia , Tiazoles/metabolismo , Tionas/metabolismo , Actinobacteria/enzimología , Actinobacteria/genética , Proteínas Bacterianas/biosíntesis , Proteínas Bacterianas/genética , Biología Computacional
19.
Environ Microbiol ; 21(11): 4270-4282, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31435987

RESUMEN

Acyltransferase (AT)-less type I polyketide synthases (PKSs) produce complex natural products due to the presence of many unique tailoring enzymes. The 3-hydroxy-3-methylglutaryl coenzyme A synthases (HCSs) are responsible for ß-alkylation of the growing polyketide intermediates in AT-less type I PKSs. In this study, we discovered a large group of HCSs, closely associated with the characterized and orphan AT-less type I PKSs through in silico genome mining, sequence and genome neighbourhood network analyses. Using HCS-based probes, the survey of 1207 in-house strains and 18 soil samples from different geographic locations revealed the vast diversity of HCS-containing AT-less type I PKSs. The presence of HCSs in many AT-less type I PKSs suggests their co-evolutionary relationship. This study provides a new probe to study the abundance and diversity of AT-less type I PKSs in the environment and microbial strain collections. Our study should inspire future efforts to discover new polyketide natural products from AT-less type I PKSs.


Asunto(s)
Hidroximetilglutaril-CoA Sintasa/análisis , Sintasas Poliquetidas/análisis , Suelo/química , Bacterias/genética , Productos Biológicos/análisis , Genoma Bacteriano , Microbiología del Suelo
20.
Int J Syst Evol Microbiol ; 69(2): 567-571, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30605074

RESUMEN

A novel Gram-positive bacterium, designated strain YIM PH21725T, was isolated from a sample of rhizospheric soil of Panaxnotoginseng cultivated in Anning, Yunnan. The strain contained meso-diaminopimelic acid in the cell-wall peptidoglycan. The main fatty acids identified were C17 : 0, iso-C15 : 0, iso-C16 : 0 and C16 : 0. The main menaquinone was MK-9 (H4). The polar lipids included phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol mannoside, phosphatidylinositol, phospholipids and phospholipids of an unidentified structure containing glucosamine. The G+C content of genomic DNA was 69.43 mol%. On the basis of its 16S rRNA gene sequence, strain YIM PH21725T should belong to the genus Amycolatopsis, and was closely related to Amycolatopsis sulphurea DSM 46092T (98.57 %), Amycolatopsis jejuensis JCM13280T (97.27 %), Amycolatopsis jiangsuensis KCTC 19885T (96.88 %) and Amycolatopsis ultiminotia JCM 16989T (96.8 %). The phenotypic, chemotaxonomic, phylogenetic and digital DNA-DNA hybridization results clearly indicated that strain YIM PH21725T represents a novel species of the genus Amycolatopsis, for which the name Amycolatopsispanacis sp. nov. is proposed. The type strain is YIM PH21725T (=CCTCC AA 2017044T=KCTC 49031T=DSM 105902T).


Asunto(s)
Actinobacteria/clasificación , Panax notoginseng/microbiología , Filogenia , Microbiología del Suelo , Actinobacteria/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , Pared Celular/química , China , ADN Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Grasos/química , Hibridación de Ácido Nucleico , Peptidoglicano/química , Fosfolípidos/química , ARN Ribosómico 16S/genética , Rizosfera , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/química
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