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1.
Opt Express ; 32(12): 20449-20458, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38859426

ABSTRACT

Liquid crystal (LC) gratings have played important roles in light field control due to the advantages of being lightweight, low cost, having no moving parts, and low power consumption. However, the chromatic aberration limits the bandwidth of the LC device and affects the efficiency of the grating. To solve the chromatic aberration issue, a broadband wavelength designable achromatic grating is proposed. Different grating structures are integrated into a single-layer templated cholesteric liquid crystal (CLC) device, and the achromatic diffraction wavelength of the grating can be freely designed from the visible spectral region to the infrared range within the Bragg reflection band of the CLCs. The diffraction intensity of different orders can be changed with the electric field applied to meet the need for dynamic modulation. This grating shows suitable potential applications in optical communication and displays.

2.
Hemodial Int ; 28(2): 236-240, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38385980

ABSTRACT

Acute upper limb ischemia is a rare, potentially limb- or life-threatening vascular emergency that may lead to limb dysfunction or amputation. We present a patient undergoing maintenance hemodialysis who was hospitalized for arteriovenous graft thrombus complicated by acute upper limb ischemia arising from thrombus shedding to the fingertip arteries during thrombolysis. We successfully restored fingertip arterial patency, avoided amputation, and recovered the function of the arteriovenous graft by precise thrombolysis, anticoagulation, correction of arteriospasm, and percutaneous transluminal angioplasty. This case provides a basis for vascular access surgeons to treat acute upper limb ischemia caused by thromboembolism similarly.


Subject(s)
Renal Dialysis , Thrombosis , Humans , Ischemia/etiology , Thrombosis/drug therapy , Thrombosis/etiology , Thrombolytic Therapy , Treatment Outcome , Vascular Patency , Retrospective Studies
3.
BMJ Open ; 13(11): e078051, 2023 11 02.
Article in English | MEDLINE | ID: mdl-37918934

ABSTRACT

OBJECTIVE: To identify profiles of nurses' perceived professional benefits as well as their predictors. DESIGN: Cross-sectional study. SETTING: The study was carried out online in China. METHODS: From 6 July to 27 July 2022, a total of 1309 registered nurses participated in the survey by convenient sampling. We collected the Nurses' Perceived Professional Benefits Questionnaire and demographic data. Using latent profile analysis (LPA), subgroups of nurses' perceived professional benefits were identified. Moreover, univariate and multinomial logistic regression analyses were conducted to find the factors that were linked with the profiles. RESULTS: The survey was validly completed by 1309 nurses, with a 92.9% effective return rate. The findings of the LPA demonstrated three unique profiles: low-perceived professional benefits (11.8%), moderate-perceived professional benefits (57.1%) and high-perceived professional benefits (31.1%). There was a correlation between marital status, the number of night shifts per month and leadership role. CONCLUSIONS: According to our research, registered nurses have three unique professional benefit profiles. In order to sustain the nursing workforce, despite the fact that nurses get a high level of professional benefits, interventions are necessary to increase nurses' perception of their professional value.


Subject(s)
Burnout, Professional , Nurses , Nursing Staff, Hospital , Nursing Staff , Humans , Cross-Sectional Studies , China , Surveys and Questionnaires , Job Satisfaction
4.
J Nat Prod ; 86(3): 589-595, 2023 03 24.
Article in English | MEDLINE | ID: mdl-36563017

ABSTRACT

Three diphenyl ethers (1-3) and a cyclopentenone (4), together with seven known compounds (5-11), were isolated from the fermentation broth of the marine sediment-derived fungus Spiromastix sp. SCSIO F190. Compounds 3 and 4 were found to exist as a pair of atropisomers (3a, 3b) and racemates (4a, 4b), respectively. The planar structures of compounds 1-4 were elucidated on the basis of NMR and HRESIMS data sets. The absolute configurations of 2 and 3 were determined by spectroscopic and single-crystal X-ray diffraction analyses, whereas the configuration of 4 was determined by spectroscopic and chiral analyses. All compounds, except for 4 and 11, displayed activities against various pathogenic bacteria. Notably, compounds 1-4, especially 1, exhibited strong activity against Gram-positive bacteria, including methicillin-resistant bacterial strains of Staphylococcus aureus (MRSA), Enterococcus faecalis ATCC 29212, and Bacillus subtilis BS01, with MIC values ranging from 0.5 to 4 µg/mL. Moreover, the structure-activity relationship analyses of the active compounds and their analogues revealed the critical structural features correlating to the observed antimicrobial activities, herein providing insights for antimicrobial drug development.


Subject(s)
Anti-Infective Agents , Methicillin-Resistant Staphylococcus aureus , Polyketides , Anti-Bacterial Agents/chemistry , Polyketides/chemistry , Molecular Structure , Fungi , Magnetic Resonance Spectroscopy , Bacteria , Microbial Sensitivity Tests
5.
Polymers (Basel) ; 16(1)2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38201747

ABSTRACT

Cholesteric liquid crystals (CLCs) exhibit selective reflection due to their self-assembled helical superstructures. Reconfigurable templates can achieve integration functions via inducing processes of molecular assemblies. Here we demonstrate temperature self-adaptive and color-adjustable smart windows using CLCs, which are fabricated via the templating method and exhibit simultaneous reflections in the visible and infrared spectra. Reflection bands formed by the refilled CLC materials can be adjusted reversibly both upon thermal and electrical actuation. In CLC with adjustable reflection in the infrared, the central wavelength of the infrared reflection band can be adjusted from 950 nm to 1305 nm via temperature, and from 1150 nm to 950 nm via electric field. A temperature variation of 10.3 °C within 55 s was induced by the single-layer templated CLC cell, and a comfortable temperature range could be effectively maintained by the CLC cell in a varied environment. In CLC with dynamic color in the visible spectrum, color shifts from 530 nm to 650 nm tuned by temperature and from 530 nm to 440 nm adjusted by electric field were obtained. Temperature-responsive reflection in the infrared spectrum contributes to automatic thermal management, and electric-field-induced band shift in the visible spectrum enables active dynamic color adjustment. The presented templated CLC smart windows show considerable potential in energy conservation and biological clock regulation fields.

6.
Polymers (Basel) ; 14(22)2022 Nov 13.
Article in English | MEDLINE | ID: mdl-36433026

ABSTRACT

An optical filter is one of the indispensable devices in massive and high-speed communication, optical signal processing, and display. Twist-structure liquid crystals, cholesteric liquid crystals, blue-phase liquid crystals, and sphere-phase liquid crystals show potential application in optical filters originating from the periodic nanostructures. Wavelength and bandwidth tuning can be controlled via temperature, electric fields, light, angle, spatial control, and templating technology. In this review, we discuss the recent developments of twist-structure liquid crystal filters.

7.
Mar Drugs ; 20(8)2022 Aug 21.
Article in English | MEDLINE | ID: mdl-36005541

ABSTRACT

Four actinomycete strains isolated from the coral Acropora austera and coral sand samples from the South China Sea, were found to produce a series of halogenated compounds baring similar ultraviolet absorption based on the analysis of HPLC and LC-MS. The production titers of halogenated compounds from Streptomyces diacarni SCSIO 64983 exceeded those of other similar strains leading us to focus on SCSIO 64983. Four new thiocarbazomycins A-B (1-2), chlocarbazomycin E (3), and brocarbazomycin A (4), together with three known chlocarbazomycins A-C (5-7) containing a carbazole core were identified, and their structures were determined using a combination of spectroscopic analysis including HRESIMS, 1D and 2D NMR. Structurally speaking, compounds 1 and 2 have the rare sulfur-containing carbazole nuclei, and 3 and 4 contain Cl and Br atoms, respectively. Although these compounds have not yet been found to have obvious biological activity, their discovery highlights the role of molecular libraries in subsequent drug discovery campaigns.


Subject(s)
Actinobacteria , Anthozoa , Actinobacteria/chemistry , Actinomyces , Animals , Carbazoles , Coral Reefs , Sand
8.
Front Chem ; 9: 774555, 2021.
Article in English | MEDLINE | ID: mdl-34778219

ABSTRACT

Tuberculosis (TB) is still a global disease threatening people's lives. With the emergence of multi-drug-resistant Mycobacterium tuberculosis the prevention and control of tuberculosis faces new challenges, and the burden of tuberculosis treatment is increasing among the world. Ilamycins are novel cyclopeptides with potent anti-TB activities, which have a unique target protein against M. tuberculosis and drug-resistant strains. Herein, ilamycin F, a major secondary metabolite isolated from the marine-derived mutant strain Streptomyces atratus SCSIO ZH16 ΔilaR, is used as a scaffold to semi-synthesize eighteen new ilamycin derivatives (ilamycin NJL1-NJL18, 1-18). Our study reveals that four of ilamycin NJLs (1, 6, 8, and 10) have slightly stronger anti-TB activities against Mtb H37Rv (minimum inhibitory concentration, 1.6-1.7 µM) compared with that of ilamycin F on day 14th, but obviously display more potent activities than ilamycin F on day 3rd, indicating anti-TB activities of these derivatives with fast-onset effect. In addition, cytotoxic assays show most ilamycin NJLs with low cytotoxicity except ilamycin NJL1 (1). These findings will promote the further exploration of structure-activity relationships for ilamycins and the development of anti-TB drugs.

9.
J Nat Prod ; 84(8): 2217-2225, 2021 08 27.
Article in English | MEDLINE | ID: mdl-34270246

ABSTRACT

Through precursor-directed biosynthesis, feeding halogenated (F-, Cl-, Br-, I-) or methoxy-substituted 4-methyl-3-hydroxyanthranilic acid (4-MHA) analogues to the acnGHLM-deleted mutant strain of Streptomyces costaricanus SCSIO ZS0073 led to the production of ten new actinomycin analogues (4-13). Several of the actinomycin congeners displayed impressive antimicrobial activities, with MIC values spanning 0.06-64 µg/mL to clinically derived antibiotic resistant pathogens, including Staphylococcus aureus, Enterococcus faecium, and Candida albicans, with low cytotoxicity.


Subject(s)
Anti-Infective Agents/pharmacology , Dactinomycin/analogs & derivatives , Streptomyces/metabolism , Candida albicans/drug effects , Cell Line, Tumor , Enterococcus faecium/drug effects , Halogenation , Humans , Microbial Sensitivity Tests , Molecular Structure , Staphylococcus aureus/drug effects , Streptomyces/genetics
10.
Commun Biol ; 3(1): 527, 2020 09 23.
Article in English | MEDLINE | ID: mdl-32968175

ABSTRACT

Fungal-bacterial associations are present in nature, playing important roles in ecological, evolutionary and medicinal processes. Here we report a fungus-bacterial symbiont from marine sediment. The bacterium lives inside the fungal mycelium yet is robust enough to survive independent of its host; the independently grown bacterium can infect the fungal host in vitro and continue to grow progenitively. The bacterial symbiont modulates the fungal host to biosynthesize a polyketide antimicrobial, spiromarmycin. Spiromarmycin appears to endow upon the symbiont pair a protective/defensive means of warding off competitor organisms, be they prokaryotic or eukaryotic microorganisms. Genomic analyses revealed the spiromarmycin biosynthetic machinery to be encoded, not by the bacterium, but rather the fungal host. This unique fungal-bacterial symbiotic relationship and the molecule/s resulting from it dramatically expand our knowledge of marine microbial diversity and shed important insights into endosymbionts and fungal-bacterial relationships.


Subject(s)
Actinobacteria/genetics , Alcaligenes faecalis/genetics , Aquatic Organisms/genetics , Multigene Family/physiology , Actinobacteria/metabolism , Actinobacteria/physiology , Alcaligenes faecalis/metabolism , Alcaligenes faecalis/physiology , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/pharmacology , Geologic Sediments/microbiology , Microbial Sensitivity Tests , Symbiosis , Up-Regulation
11.
J Nat Prod ; 83(5): 1646-1657, 2020 05 22.
Article in English | MEDLINE | ID: mdl-32324401

ABSTRACT

Tuberculosis (TB) ranks as the leading cause of death from a single infectious agent (ranking more lethal than HIV/AIDS) over the course of the past decade. More concerning is that reports of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of TB have been dramatically increasing. It continues to become ever more clear that novel anti-TB drugs with improved efficacies and reduced toxicities are urgently needed. We report here the discovery of 12 new ilamycin analogues, ilamycins G-R (1-12), bearing various nonproteinogenic amino acids, along with ilamycins E1 (13) and F (14), from a 200 L scale culture of the marine-derived mutant actinomycete Streptomyces atratus SCSIO ZH16 ΔilaR. Importantly, bioassays against Mycobacterium tuberculosis H37Rv revealed that all 12 new agents displayed antitubercular activities with MIC values ranging from 0.0096 to 10 µM. The structures of 1-12 were elucidated on the basis of HRESIMS, 1D and 2D NMR, and X-ray single-crystal diffraction studies. In addition, compound 10 was found to be moderately cytotoxic against a panel of tumor human cell lines. From these data we can formulate tentative structure-activity relationships for the antitubercular and antitumor activities of the ilamycins.


Subject(s)
Antineoplastic Agents/pharmacology , Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Streptomyces/chemistry , Antineoplastic Agents/chemistry , Antitubercular Agents/chemistry , Cell Line, Tumor , Drug Design , Humans , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship
12.
J Nat Prod ; 83(5): 1666-1673, 2020 05 22.
Article in English | MEDLINE | ID: mdl-32338895

ABSTRACT

Two new cyclodecapeptides, atratumycins B (1) and C (2), containing substituted cinnamoyl side chains were generated by converging elements of the atratumycin (3) and atrovimycin (4) biosynthetic pathways. The structures of 1 and 2 were determined on the basis of HRESIMS, 1D and 2D NMR data, and X-ray single-crystal diffraction studies. Atratumycin B (1) is active against autoluminescent Mycobacterium tuberculosis H37Rv, displaying a minimum inhibitory concentration of 3.1 µg/mL (2.3 µM).


Subject(s)
Antitubercular Agents/pharmacology , Depsipeptides/chemistry , Mycobacterium tuberculosis/chemistry , Streptomyces/chemistry , Antitubercular Agents/chemistry , Biosynthetic Pathways , Crystallography, X-Ray , Depsipeptides/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Mycobacterium tuberculosis/metabolism
13.
Chem Biodivers ; 17(4): e2000057, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32091654

ABSTRACT

Two julichrome monomers, julichromes Q11 (1) and Q12 (2), along with five known julichromes (Q10 , Q3 ⋅ 5 , Q3 ⋅ 3 , Q6 ⋅ 6 , Q6 , 3-7) and four known anthraquinones (chrysophanol, 4-acetylchrysophanol, islandicin, huanglongmycin A, 8-11), were isolated from the marine gastropod mollusk Batillaria zonalis-associated Streptomyces sampsonii SCSIO 054. This is the first report of julichromes isolated from a marine source. Extensive dissection of 1D and 2D NMR datasets combined with X-ray crystallography enabled rigorous elucidation of the previously reported configurations of julichrome Q3 ⋅ 5 (4) and related julichrome Q3 ⋅ 3 (5); both of the configuration at C(9) needs to be revised. In addition, julichrome Q12 (2) was found to display antibacterial activity against Micrococcus luteus and Bacillus subtilis with MICs of 2.0 and 8.0 µg mL-1 ; four compounds (1, 3, 6, 7) also showed inhibitory activities against an array of methicillin-resistant Staphylococcus aureus, S. aureus and S. simulans AKA1 with MIC values ranging from 8 to 64 µg mL-1 .


Subject(s)
Anti-Bacterial Agents/chemistry , Gastropoda/microbiology , Naphthalenes/chemistry , Streptomyces/chemistry , Animals , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Bacillus subtilis/drug effects , Crystallography, X-Ray , Microbial Sensitivity Tests , Micrococcus luteus/drug effects , Molecular Conformation , Naphthalenes/isolation & purification , Naphthalenes/pharmacology , Phylogeny , Stereoisomerism , Streptomyces/classification , Streptomyces/metabolism
14.
Chem Biodivers ; 17(1): e1900560, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31769919

ABSTRACT

Borrelidins M-O (1-3), along with four previously known family members (4-7), were isolated from marine pulmonated mollusks Onchidium sp. associated Streptomyces olivaceus SCSIO LO13. The structures of 1-3 were elucidated by extensive spectral analyses of HR-ESI-MS, 1D and 2D NMR data. In addition, the cytotoxic and antibacterial activities of 1-7 were evaluated enabling us to propose some tentative structure-activity relationships (SARs), especially those involving modifications at C(22) and the moieties at C(7) and C(8) of the borrelidin scaffold.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/pharmacology , Gastropoda/chemistry , Streptomyces/chemistry , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Fatty Alcohols/chemistry , Fatty Alcohols/isolation & purification , Fatty Alcohols/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship
15.
Sci Rep ; 9(1): 16900, 2019 Nov 15.
Article in English | MEDLINE | ID: mdl-31729452

ABSTRACT

A polarization-independent blue phase liquid crystal on silicon (BPLCoS) device with low operation voltage for 2π phase depth is demonstrated. With optimized reflection structure and two reflection films, the incident light may experience multifold optical path and 2π phase depth can be obtained. For the polarization-independence, an inclined electric field made by periodical gradient voltage is applied on the blue phase liquid crystal (BPLC) to match the light propagation direction. With the structure, the operation voltage can be lowered to 5.5 V in simulation and 5.9 V in experiment for 2π phase modulation at 1550 nm. The proposed device shows great potential for communication and imaging systems.

16.
J Nat Prod ; 82(12): 3366-3371, 2019 12 27.
Article in English | MEDLINE | ID: mdl-31765156

ABSTRACT

Three new kendomycin analogues, kendomycins B-D (1-3), were discovered from the marine-derived actinomycete Verrucosispora sp. SCSIO 07399. The structures of 1-3 were elucidated using diverse spectroscopic data analyses, X-ray crystallography, and semisynthetic derivatization. In vitro antimicrobial assays revealed that 1-3 all display good antibacterial activities against six Gram-positive bacteria with MIC values ranging from 0.5 to 8.0 µg/mL. Additionally, 1-3 were found to be moderately cytotoxic against MGC803, A549, HeLa, HepG2, MCF-7, and RKO human tumor cell lines; IC50 values ranged from 2.2 to 44 µM.


Subject(s)
Antineoplastic Agents/pharmacology , Marine Biology , Micromonosporaceae/chemistry , Rifabutin/analogs & derivatives , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Chromatography, High Pressure Liquid , Crystallography, X-Ray , Gram-Positive Bacteria/drug effects , Humans , Molecular Structure , Rifabutin/chemistry , Rifabutin/pharmacology , Spectrum Analysis/methods
17.
Mar Drugs ; 17(10)2019 Sep 29.
Article in English | MEDLINE | ID: mdl-31569487

ABSTRACT

Atratumycin is a cyclodepsipeptide with activity against Mycobacteria tuberculosis isolated from deep-sea derived Streptomyces atratus SCSIO ZH16NS-80S. Analysis of the atratumycin biosynthetic gene cluster (atr) revealed that its biosynthesis is regulated by multiple factors, including two LuxR regulatory genes (atr1 and atr2), two ABC transporter genes (atr29 and atr30) and one Streptomyces antibiotic regulatory gene (atr32). In this work, three regulatory and two transporter genes were unambiguously determined to provide positive, negative and self-protective roles during biosynthesis of atratumycin through bioinformatic analyses, gene inactivations and trans-complementation studies. Notably, an unusual Streptomyces antibiotic regulatory protein Atr32 was characterized as a negative regulator; the function of Atr32 is distinct from previous studies. Five over-expression mutant strains were constructed by rational application of the regulatory and transporter genes; the resulting strains produced significantly improved titers of atratumycin that were ca. 1.7-2.3 fold greater than wild-type (WT) producer. Furthermore, the atratumycin gene cluster was successfully expressed in Streptomyces coelicolor M1154, thus paving the way for the transfer and recombination of large DNA fragments. Overall, this finding sets the stage for understanding the unique biosynthesis of pharmaceutically important atratumycin and lays the foundation for generating anti-tuberculosis lead compounds possessing novel structures.


Subject(s)
Aquatic Organisms/genetics , Bacterial Proteins/genetics , Depsipeptides/biosynthesis , Gene Regulatory Networks , Streptomyces/genetics , Antitubercular Agents , Aquatic Organisms/metabolism , Bacterial Proteins/metabolism , Cloning, Molecular , Computational Biology , Depsipeptides/genetics , Depsipeptides/pharmacology , Gene Expression Regulation, Bacterial , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Multigene Family , Mycobacterium tuberculosis/drug effects , Sequence Alignment , Streptomyces/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
18.
Mar Drugs ; 17(8)2019 Jul 26.
Article in English | MEDLINE | ID: mdl-31357504

ABSTRACT

Candida albicans is a type of commensal fungi which causes serious infections in immunocompromised patients and contributes to high mortality. In the present study, we identified that the extract from Streptomyces olivaceus SCSIO T05 inhibited hypha and biofilm formation of C. albicans. Seven compounds were isolated and evaluated for their effects on the biological functions and virulence of C. albicans. Two leading compounds, compound 1 (sorbicillin) and compound 2 (3-methyl-N-(2'-phenethyl)-butyrylamide) were identified as exhibiting strong activity against C. albicans morphological transition, adhesion activity, cytotoxicity, and adhesion to human cells, in a dose-dependent manner. Notably, compound 2 inhibited C. albicans infection in mouse oral mucosal models. Transcriptomic analysis and real-time PCR results revealed that compound 2 most likely inhibited the biological functions of C. albicans cells by regulating the expression levels of HWP1, TEC1, ALS1, IFD6, and CSH1, which are associated with filament formation and cell adhesion. Our results suggest that the candidate compounds present excellent efficacy against C. albicans pathogenicity and that they can be developed as potential options for the clinical treatment of candidiasis.


Subject(s)
Antifungal Agents/pharmacology , Candida albicans/drug effects , Morphogenesis/drug effects , Streptomyces/chemistry , Virulence/drug effects , A549 Cells , Animals , Biofilms/drug effects , Candida albicans/genetics , Candidiasis/drug therapy , Candidiasis/microbiology , Cell Adhesion/drug effects , Cell Line, Tumor , Fungal Proteins/genetics , Humans , Hyphae/drug effects , Male , Mice , Mice, Inbred BALB C , Mouth Mucosa/microbiology , Resorcinols/pharmacology , Transcriptome/drug effects
19.
Org Lett ; 21(8): 2634-2638, 2019 04 19.
Article in English | MEDLINE | ID: mdl-30958008

ABSTRACT

Atrovimycin (1), a cyclodepsipeptide containing a unique vicinal-hydroxylated cinnamic acyl chain, was isolated and elucidated from Streptomyces atrovirens LQ13. The biosynthetic pathway of 1 was achieved, revealing cytochrome P450 (Avm43) and epoxide hydrolase (Avm29) enzymes constructing the vicinal-dihydroxy substitution, as well as a tailoring P450 (Avm28) enzyme catalyzing ß-hydroxylation of the l-Phe moiety. Atrovimycin shows in vitro antifungal activity and antitubercular activity against Mycobacterium tuberculosis H37Rv both in vitro (with MIC of 2.5 µg/mL) and in vivo.


Subject(s)
Antifungal Agents/metabolism , Antitubercular Agents/metabolism , Depsipeptides/biosynthesis , Antifungal Agents/chemistry , Antitubercular Agents/pharmacology , Biocatalysis , Biosynthetic Pathways , Cytochrome P-450 Enzyme System/metabolism , Depsipeptides/chemistry , Epoxide Hydrolases/metabolism , Hydroxylation , Mycobacterium tuberculosis/drug effects , Streptomyces/metabolism , Structure-Activity Relationship
20.
Mar Drugs ; 17(4)2019 Apr 23.
Article in English | MEDLINE | ID: mdl-31018504

ABSTRACT

Bioactive secondary metabolites from Streptomycetes are important sources of lead compounds in current drug development. Streptomyces costaricanus SCSIO ZS0073, a mangrove-derived actinomycete, produces actinomycin D, a clinically used therapeutic for Wilm's tumor of the kidney, trophoblastic tumors and rhabdomyosarcoma. In this work, we identified the actinomycin biosynthetic gene cluster (BGC) acn by detailed analyses of the S. costaricanus SCSIO ZS0073 genome. This organism produces actinomycin D with a titer of ~69.8 µg mL-1 along with traces of actinomycin Xoß. The acn cluster localized to a 39.8 kb length region consisting of 25 open reading frames (ORFs), including a set of four genes that drive the construction of the 4-methyl-3-hydroxy-anthranilic acid (4-MHA) precursor and three non-ribosomal peptide synthetases (NRPSs) that generate the 4-MHA pentapeptide semi-lactone, which, upon dimerization, affords final actinomycin D. Furthermore, the acn cluster contains four positive regulatory genes acnWU4RO, which were identified by in vivo gene inactivation studies. Our data provide insights into the genetic characteristics of this new mangrove-derived actinomycin D bioproducer, enabling future metabolic engineering campaigns to improve both titers and the structural diversities possible for actinomycin D and related analogues.


Subject(s)
Biosynthetic Pathways/physiology , Dactinomycin/metabolism , Streptomyces/metabolism , Multigene Family/physiology , Peptide Synthases/metabolism , ortho-Aminobenzoates/metabolism
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