Showing papers in "The Journal of Antibiotics in 2011"
TL;DR: This work has shown that the c group of Gram-negative gliding bacteria, has a long history of cosmopolitan occurrence, and has great biodiversity despite the absence of sexual reproduction, which may be reflected in the wide spectrum of its secondary metabolites.
Abstract: The c group of Gram-negative gliding bacteria, has a long history of cosmopolitan occurrence. It has great biodiversity despite the absence of sexual reproduction. This wide biodiversity may be reflected in the wide spectrum of its secondary metabolites. These cyanobacterial secondary metabolites are biosynthesized by a variety of routes, notably by non-ribosomal peptide synthetase or polyketide synthetase systems, and show a wide range of biological activities including anticancer, antibacterial, antiviral and protease inhibition activities. This high degree of chemical diversity in cyanobacterial secondary metabolites may thus constitute a prolific source of new entities leading to the development of new pharmaceuticals.
286 citations
TL;DR: The 20 new antibiotics launched since 2000 and the 40 compounds currently in active clinical development are listed and the NP or synthetic derivation is discussed, with activity against Gram-negative bacteria highlighted.
Abstract: The emergence of multi-drug-resistant bacteria and the lack of new antibiotics in the antibiotic drug development pipeline, especially those with new modes of action, is a major health concern. This review lists the 20 new antibiotics launched since 2000 and records the 40 compounds currently in active clinical development. Compounds in the pipeline from new antibiotic classes are reviewed in detail with reference to their development status, mode of action, spectrum of activity and lead discovery. In addition, the NP or synthetic derivation is discussed, with activity against Gram-negative bacteria highlighted.
254 citations
TL;DR: This review highlights the development of materials used in extended-release formulation and nanoparticles for antibiotic delivery and provides an overview of the antibiotic extended- release products that have provided clinical benefit or are undergoing the clinical trial.
Abstract: To maintain antimicrobial activity, frequent administration of conventional formulations of many antibiotics with short half-life is necessary. Otherwise, concentration under MIC occurs frequently in the course of anti-infective treatment, which induces antibiotic resistance. By maintaining a constant plasma drug concentration over MIC for a prolonged period, extended-release dosage forms maximize the therapeutic effect of antibiotics while minimizing antibiotic resistance. Another undoubted advantage of extended-release formulation is improved patient compliance. For better release properties, many materials have been introduced into the matrix and coating extended-release system in the past few years. Materials that have been widely used in industry are hydrophilic matrix materials such as hydroxypropylmethylcellulose. The excellent biocompatibility and extensive laboratory studies provide biodegradable polymers great potential for industrial applications. In addition, it seems like the researches on tailored materials that are obtained by chemical modification of the existing materials or combination of different carriers in physical mixtures have a long way to go. Meanwhile, with the development of polymers and inorganic porous nanocarriers, nanotechnology is applied increasingly for the extended delivery of antibiotics. This review highlights the development of materials used in extended-release formulation and nanoparticles for antibiotic delivery. We also provide an overview of the antibiotic extended-release products that have provided clinical benefit or are undergoing the clinical trial.
248 citations
TL;DR: Romidepsin (Istodax), a selective inhibitor of histone deacetylases (HDACs), was approved for the treatment of cutaneous T-cell lymphoma in November 2009 by the US Food and Drug Administration and analogs are sought to create synthetically accessible alternatives.
Abstract: Romidepsin (Istodax), a selective inhibitor of histone deacetylases (HDACs), was approved for the treatment of cutaneous T-cell lymphoma in November 2009 by the US Food and Drug Administration. This unique natural product was discovered from cultures of Chromobacterium violaceum, a Gram-negative bacterium isolated from a Japanese soil sample. This bicyclic compound acts as a prodrug, its disulfide bridge being reduced by glutathione on uptake into the cell, allowing the free thiol groups to interact with Zn ions in the active site of class I and II HDAC enzymes. Due to the synthetic complexity of the compound, as well as the low yield from the producing organism, analogs are sought to create synthetically accessible alternatives. As a T-cell lymphoma drug, romidepsin offers a valuable new treatment for diseases with few effective therapies.
240 citations
TL;DR: Members of the genera Phellinus and Inonotus are well-known medicinal fungi (mushrooms) and have been used in treatment of cancer, diabetes, bacterial and viral infections and ulcer, and were shown to produce a large and diverse range of styrylpyrone-type polyphenol pigments that exhibited various biological activities.
Abstract: Members of the genera Phellinus and Inonotus, including P. linteus, P. igniarius, P. ribis, I. obliquus and I. xeranticus are well-known medicinal fungi (mushrooms) and have been used in treatment of cancer, diabetes, bacterial and viral infections and ulcer. Adverse effects of these medicinal mushrooms have not yet been reported, indicating the safe nature of these mushrooms. Polysaccharides, particularly β-glucan, are considered the compounds responsible for the biological activity of medicinal mushrooms. However, there is only a limited amount of evidence to indicate that polysaccharides are in fact responsible for the biological effects of these medicinal mushrooms. Recently, many research groups have begun identification of active low-MW compounds in medicinal mushrooms, with a focus on the yellow polyphenol pigments, which are composed of a styrylpyrone class of compounds. Interestingly, a representative group of medicinal fungi, including P. linteus, P. igniarius, P. ribis, I. obliquus and I. xeranticus were shown to produce a large and diverse range of styrylpyrone-type polyphenol pigments that exhibited various biological activities, including anti-oxidative, anti-inflammatory, cytotoxic, anti-platelet aggregation, anti-diabetic, anti-dementia and anti-viral effects. Styrylpyrone pigments in mushrooms are thought to have a role similar to that of flavonoids in plants. The unique and unprecedented carbon skeleton of fused styrylpyrone might be an attractive molecular scaffold for pharmacological applications. In this review, the structural diversity, biological effects and biogenesis of styrylpyrone-class polyphenols from medicinal fungi are described.
124 citations
TL;DR: It is reaffirmed by this report that important pharmaceuticals can be produced by endophytic microbes, and these molecules appear to be mimetic to their host origin, and the bioactive principles of medicinal plants can be enhanced by isolating and identifying the endophytes, thereby showing the importance of preserving the biodiversity of these plants.
Abstract: The endophytic fungus Periconia sp. produces piperine (5-(3, 4-methylenedioxyphenyl)-1-piperidinopent-2, 4-dien-1-one) under liquid culture. This is the first report of the alternative source for this chemical other than its host, Piper longum. The highly functionalized fungus-derived piperine exhibits strong antimycobacterial activity against Mycobacterium tuberculosis and M. smegmetis with minimum inhibitory concentrations of 1.74 and 2.62 μg ml−1, respectively. The compound was crystallized and the structure was elucidated by single-crystal X-ray crystallography. This finding is of significance as piperine is a potential cancer preventative agent. It is reaffirmed by this report that important pharmaceuticals can be produced by endophytic microbes, and these molecules appear to be mimetic to their host origin. Therefore, we can enhance the bioactive principles of medicinal plants by isolating and identifying the endophytes, thereby showing the importance of preserving the biodiversity of these plants.
92 citations
TL;DR: A novel far-red fluorescent stain, Vybrant DyeCycle Ruby (DCR) for the flow cytometric analysis of fluoroquinolone (ciprofloxacin) bacteriostatic and bactericidal activities in Escherichia coli proved to be specific for bacterial DNA.
Abstract: As common microbiological methods for the assessment of bacteriostatic or bactericidal activities are very time-consuming, in this work we describe that the use of a novel far-red fluorescent stain, Vybrant DyeCycle Ruby (DCR) for the flow cytometric analysis of fluoroquinolone (ciprofloxacin) bacteriostatic and bactericidal activities in Escherichia coli proved to be specific for bacterial DNA and, after ciprofloxacin exposure, DNA distribution analysis was achieved using a 7.5 μM DCR concentration to stain 5 × 105 ethanol-fixed bacterial cells. The analysis of the bacterial DNA histograms obtained from the ciprofloxacin concentrations tested, enabled the distinction between ciprofloxacin bacteriostatic and bactericidal activities.
86 citations
TL;DR: In vivo infection study using mice clearly indicated that the administration of aurodox allowed the mice to survive a lethal dose of Citrobactor rodentium, a model bacterium for human pathogens such as EPEC, and directly demonstrated for the first time that this putative T3SS inhibitor can be applied as a novel class of anti-infective agents.
Abstract: The type III secretion system (T3SS) is highly conserved in many Gram-negative pathogenic bacteria and functions as an injector of bacterial proteins (effectors) into host cells. T3SSs are involved in establishing disease processes, but this machinery is not essential for bacterial growth or homeostasis. Thus, T3SS is expected to be a candidate therapeutic target, and inhibitors of T3SSs could potentially reduce virulence without causing bacterial death, thereby avoiding any subsequent development of resistance. We identified a linear polyketide compound, aurodox, as a specific T3SS inhibitor from the culture broth of Streptomyces sp. using a screening system for the T3SS-mediated hemolysis of enteropathogenic Escherichia coli (EPEC) established by our group. Aurodox strongly inhibited T3SS-mediated hemolysis with an IC50 value of 1.5 μg ml−1 without affecting bacterial growth in liquid media. We also demonstrated that aurodox specifically inhibits the secretion of type III-secreted proteins such as EspB, EspF and Map, without affecting the expression of the housekeeping protein GroEL. Furthermore, an in vivo infection study using mice clearly indicated that the administration of aurodox allowed the mice to survive a lethal dose of Citrobactor rodentium, a model bacterium for human pathogens such as EPEC. Thus, our in vivo study directly demonstrated for the first time that this putative T3SS inhibitor can be applied as a novel class of anti-infective agents.
85 citations
TL;DR: This review of the development of extremely potent antibacterial lantibiotic peptides for medicinal use and in food preservation focuses on the individual systems and the valuable information obtained from the many mutants produced.
Abstract: There has been great interest in the development of extremely potent antibacterial lantibiotic peptides for medicinal use and in food preservation. Of central importance to this endeavor is a strong understanding of which parts of the peptides are required for activity and which parts are expendable. Nisin, lacticin 481, nukacin ISK-1, mersacidin, lacticin 3147 and haloduracin represent many different types of lantibiotic peptides. In recent years, considerable advances toward understanding the structure–activity relationship of each of these lantibiotic systems have been achieved. This review will focus on the individual systems and the valuable information obtained from the many mutants produced.
82 citations
TL;DR: Three novel antitrypanosomal alkaloids were isolated by silica gel column chromatography and HPLC from the culture broth of a new endophytic actinomycete species and shown to be new types of pyochelin family antibiotic.
Abstract: Spoxazomicins A–C, novel antitrypanosomal alkaloids produced by an endophytic actinomycete, Streptosporangium oxazolinicum K07-0460 T
81 citations
TL;DR: The aminoshikimate pathway of formation of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of ansamycin and other antibiotics is reviewed and the AHBA synthase gene serves as a useful tool in the genetic screening for new ansamycins and other AHBA-derived natural products.
Abstract: The aminoshikimate pathway of formation of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of ansamycin and other antibiotics is reviewed. In this biosynthesis, genes for kanosamine formation have been recruited from other genomes, to provide a nitrogenous precursor. Kanosamine is then phosphorylated and converted by common cellular enzymes into 1-deoxy-1-imino-erythrose 4-phosphate, the substrate for the formation of aminoDAHP. This is converted via 5-deoxy-5-aminodehydroquinic acid and 5-deoxy-5-aminodehydroshikimic acid into AHBA. Remarkably, the pyridoxal phosphate enzyme AHBA synthase seems to have two catalytic functions: As a homodimer, it catalyzes the last reaction in the pathway, the aromatization of 5-deoxy-5-aminodehydroshikimic acid, and at the beginning of the pathway in a complex with the oxidoreductase RifL it catalyzes the transamination of UDP-3-keto-D-glucose. The AHBA synthase gene also serves as a useful tool in the genetic screening for new ansamycins and other AHBA-derived natural products.
TL;DR: The strain SCSIO 01127, isolated from the South China Sea sediment, was identified as a member of Streptomyces by the 16S rDNA sequence analysis and two new spirotetronate antibiotics lobophorins E (1) and F (2) showed antibacterial activities against Staphylococcus aureus AT CC 29213 and Enterococcus faecalis ATCC 29212.
Abstract: Lobophorins E and F, new spirotetronate antibiotics from a South China Sea-derived Streptomyces sp. SCSIO 01127
TL;DR: New bioactive secondary metabolites, called abenquines, were found in the fermentation broth of Streptomyces sp.
Abstract: New bioactive secondary metabolites, called abenquines, were found in the fermentation broth of Streptomyces sp. strain DB634, which was isolated from the soils of the Chilean highland of the Atacama Desert. They are composed of an amino acid linked to an N-acetyl-aminobenzoquinone. Isolation of the abenquines (1-4), their structure elucidation by NMR analysis and MS, as well as the kinetics of their production are presented. The abenquines show inhibitory activity against bacteria, dermatophytic fungi and phosphodiesterase type 4b. The amino acid attached to the quinone is relevant to the enzyme inhibitory activity.
TL;DR: For these antibiotics to become successful drugs, their pharmacokinetics must be improved, because they have too high a rate of clearance in the body, yielding a low degree of systematic exposure.
Abstract: Platensimycin and platencin are novel antibiotics produced by Streptomyces platensis. They are potent and non-toxic natural products active against Gram-positive pathogens, including antibiotic-resistant strains and Mycobacterium tuberculosis. They were isolated using an intriguing target-based whole-cell antisense differential sensitivity assay as inhibitors of fatty acid biosynthesis of type II. This type of biosynthesis is not present in humans. Platensimycin inhibits the elongation-condensing enzyme FabF, whereas platencin inhibits both FabF and FabH. For these antibiotics to become successful drugs, their pharmacokinetics must be improved. They have too high a rate of clearance in the body, yielding a low degree of systematic exposure. They work well when administered by continuous infusion, but this is not a useful method of delivery to patients. The two antibiotics and many analogs have been prepared by chemical synthesis. Natural congeners have also been obtained from the producing actinomycete. However, none of these molecules are as active as platensimycin and platencin. Using tools of rational metabolic engineering, superior strains have been produced making hundreds of times more antibiotic than the natural strains.
TL;DR: Testing the antibacterial properties of crotamine found that it killed several strains of Escherichia coli, with the MICs ranging from 25 to 100 μg ml−1, reinforcing the notion that crotamines originated from the β-defensin gene lineage, but has undergone significant functional diversification.
Abstract: Crotamine, a myotoxin from the venom of South American rattlesnake, is structurally related to β-defensins, antimicrobial peptides (AMPs) found in vertebrate animals. Here, we tested the antibacterial properties of crotamine and found that it killed several strains of Escherichia coli, with the MICs ranging from 25 to 100 μg ml−1. Time-kill and bacterial membrane permeabilization assays revealed that killing of bacteria by crotamine occurred within 1 h and reached the maximum by 2 h. Additionally, the anti-E. coli activity of crotamine was completely abolished with 12.5 mM NaCl. Furthermore, the three intramolecular disulfide bonds of crotamine appeared dispensable for its antibacterial activity. The reduced form of crotamine was active against E. coli as well. However, crotamine showed no or weak activity up to 200 μg ml−1 against other species of Gram-negative and Gram-positive bacteria. Crotamine showed no appreciable hemolytic activity to erythrocytes. Our studies revealed that crotamine is also an AMP that kills bacteria through membrane permeabilization. However, crotamine appears to have a narrow antibacterial spectrum, distinct from many classical β-defensins, reinforcing the notion that crotamine originated from the β-defensin gene lineage, but has undergone significant functional diversification.
TL;DR: Three new 22-membered macrolactone antibiotics, atacamycins A–C, were produced by Streptomyces sp.
Abstract: Three new 22-membered macrolactone antibiotics, atacamycins A–C, were produced by Streptomyces sp. C38, a strain isolated from a hyper-arid soil collected from the Atacama Desert in the north of Chile. The metabolites were discovered in our HPLC-diode array screening and isolated from the mycelium by extraction and chromatographic purification steps. The structures were determined by mass spectrometry and NMR experiments. Atacamycins A, B and C exhibited moderate inhibitory activities against the enzyme phosphodiesterase (PDE-4B2), whereas atacamycin A showed a moderate antiproliferative activity against adeno carcinoma and breast carcinoma cells.
TL;DR: Support for the notion that small molecules can have functions other than growth inhibition that may affect the establishment and maintenance of community dynamics in complex environments is provided.
Abstract: Approximately 2.7% of a collection of Salmonella enterica var. Typhimurium promoter-lux reporter strains showed altered transcriptional patterns when exposed to low concentrations of nine different fluoroquinolones (FQs). Even at the subinhibitory concentrations employed, all nine FQs upregulated genes involved in the SOS response, umuD, lexA, sbmC and dinP. In addition, transcriptional regulators, genes putatively associated with membrane integrity (spr), virulence (sicA) and metabolism (plsB) were affected. Using the Ames test with Salmonella strain TA102, increased mutagenicity was demonstrated in response to all the FQs tested: ciprofloxacin, moxifloxacin, levofloxacin and gatifloxacin. Transcriptional effects were largely specific to the FQ antimicrobials. Such responses are consistent with the primary mechanism of action of this class of inhibitor, namely, the introduction of DNA damage. This work provides support for the notion that small molecules can have functions other than growth inhibition that may affect the establishment and maintenance of community dynamics in complex environments.
TL;DR: Four germicidin homologs were isolated from a liquid culture of Streptomyces coelicolor A3(2) and activity of the spore extract corresponded well with the sum of the activity of each germICidin, which indicates that gericidins functions as self-germination inhibitors in S. coel Nicolor A 3(2).
Abstract: Physiological role of germicidins in spore germination and hyphal elongation in Streptomyces coelicolor A3(2)
TL;DR: This review summarizes the recent progress on the biosynthesis of fumitremorgin-type alkaloids with the identification of the biosynthetic gene clusters from genome sequences by genome mining and proof of gene function by molecular biological and biochemical investigations.
Abstract: This review summarizes the recent progress on the biosynthesis of fumitremorgin-type alkaloids; that is, the identification of the biosynthetic gene clusters from genome sequences by genome mining and proof of gene function by molecular biological and biochemical investigations.
TL;DR: Puberulic acid demonstrated a therapeutic effect in vivo, which compared well against the currently used antimalarial drugs, and thus shows promise as a leading candidate for development into a new antimalaria compound.
Abstract: In the course of screening for antimalarial agents, five tropolone compounds were isolated from the culture broth of Penicillium sp. FKI-4410. Two were known compounds, puberulic acid and stipitatic acid. Three were new analogs of puberulic acid, designated viticolins A–C. Among them, puberulic acid exhibited potent antimalarial inhibition, with IC50 values of 0.01 μg ml−1 against chloroquine-sensitive and -resistant Plasmodium falciparum strains in vitro. Furthermore, puberulic acid showed weak cytotoxicity against human MRC-5 cells, with an IC50 value of 57.2 μg ml−1. The compound also demonstrated a therapeutic effect in vivo, which compared well against the currently used antimalarial drugs, and thus shows promise as a leading candidate for development into a new antimalarial compound.
TL;DR: Antibacterial activity of violacein against Staphylococcus aureus isolated from Bovine Mastitis is inhibited and cell reprograming is observed.
Abstract: Antibacterial activity of violacein against Staphylococcus aureus isolated from Bovine Mastitis
TL;DR: In this review, the Hsp90 inhibitors that show promise for cancer therapy are summarized.
Abstract: Heat-shock protein 90 (Hsp90) inhibitor downregulates c-Myc expression and upregulates the expression of tumor repressor proteins such as p53 and pRB, inhibiting the G1/S transition and causing G2/M arrest during cell cycle progression. The cycle progression is extensively controlled by the pRB/E2F signaling pathway. E2F is released from the pRB/E2F complex with the phosphorylation of pRB by cyclin-cyclin-dependent kinase (CDK) complexes. The released E2F promotes the transcription of target genes involved in cell cycle progression. The pRB/E2F signaling pathway is controlled by DNA methyltransferase-1 (Dnmt-1). The elevated expression of Dnmt-1 has been reported in carcinomas of the colon, lung and prostate. A defect of pRB expression in Rb -/- cancer cells is caused by the aberrant methylation of CpG in the Rb promoter. The Hsp90 inhibitor disrupts the Dnmt-1/Hsp90 association and upregulates pRB expression. In this review, the Hsp90 inhibitors that show promise for cancer therapy are summarized.
TL;DR: Borrelidin, a potent antimalarial: stage-specific inhibition profile of synchronized cultures of Plasmodium falciparum.
Abstract: Borrelidin, a potent antimalarial: stage-specific inhibition profile of synchronized cultures of Plasmodium falciparum
TL;DR: Typical examples of giant linear plasmids whose involvement in antibiotic production has been studied in some detail are summarized, emphasizing their finding processes and interaction with the host chromosomes.
Abstract: Many giant linear plasmids have been isolated from Streptomyces by using pulsed-field gel electrophoresis and some of them were found to carry an antibiotic biosynthetic cluster(s); SCP1 carries biosynthetic genes for methylenomycin, pSLA2-L for lankacidin and lankamycin, and pKSL for lasalocid and echinomycin. Accumulated data suggest that giant linear plasmids have played critical roles in genome evolution and horizontal transfer of secondary metabolism. In this review, I summarize typical examples of giant linear plasmids whose involvement in antibiotic production has been studied in some detail, emphasizing their finding processes and interaction with the host chromosomes. A hypothesis on horizontal transfer of secondary metabolism involving giant linear plasmids is proposed at the end.
TL;DR: The production of these compounds, except pestalasin A, was enhanced in co-culture to be two to six times higher than in pure culture of Penicillium pinophilum FKI-5653, which was the producer ofThese compounds.
Abstract: In the course of discovering new metabolites from co-culture of Penicillium pinophilum FKI-5653 and Trichoderma harzianum FKI-5655, a new compound, designated secopenicillide C, and four known compounds, penicillide, MC-141, pestalasin A and stromemycin were isolated. The production of these compounds, except pestalasin A, was enhanced in co-culture to be two to six times higher than in pure culture of Penicillium pinophilum FKI-5653, which was the producer of these compounds.
TL;DR: Report on a PCR-specific method for the detection of this taxon, on appropriate growth conditions and on a pilot-screening program on 78 strains suggest that Actinoallomurus strains possess several pathways for secondary metabolism and represent an attractive source in the search for novel antibiotics.
Abstract: In the search for novel antibiotics, natural products continue to represent a valid source of bioactive molecules. During a program aimed at identifying previously unreported taxa of actinomycetes as potential source of novel compounds, we isolated hundreds of different representatives of a new group, initially designated as ‘Alpha’ and independently described as Actinoallomurus. We report on a PCR-specific method for the detection of this taxon, on appropriate growth conditions and on a pilot-screening program on 78 strains. The strains produce antibacterial or antifungal compounds at a relatively high frequency. Four strains were characterized in further detail: one produced the aromatic polyketide benanomicin B and its dexylosyl derivative; a second strain produced N-butylbenzenesulfonamide; a third strain was an efficient converter of soymeal isoflavonoids from soymeal constituents; and a fourth strain produced several coumermycin-related aminocoumarins, with coumermycin A2 as the major peak, and with some new congeners as minor components of the complex. These data suggest that Actinoallomurus strains possess several pathways for secondary metabolism and represent an attractive source in the search for novel antibiotics.
TL;DR: Interestingly, the isolation of actinomycetes from leaf-litter samples using the rehydration-centrifugation (RC) method proved to be the most efficient way to isolate new actinomers in Vietnam, especially the Micromonosporaceae species.
Abstract: Actinomycetes were isolated from 109 soil and 93 leaf-litter samples collected at five sites in Vietnam between 2005 and 2008 using the rehydration-centrifugation (RC) method, sodium dodecyl sulfate-yeast extract dilution method, dry-heating method and oil-separation method in conjunction with humic acid-vitamin agar as an isolation medium. A total of 1882 strains were identified as Vietnamese (VN)-actinomycetes including 1080 (57%) streptomycetes (the genus Streptomyces isolates) and 802 (43%) non-streptomycetes. The 16S ribosomal RNA gene sequences of the VN-actinomycetes were analyzed using BLAST searches. The results showed that these isolates belonged to 53 genera distributed among 21 families. Approximately 90% of these strains were members of three families: Streptomycetaceae (1087 strains, 58%); Micromonosporaceae (516 strains, 27%); and Streptosporangiaceae (89 strains, 5%). Motile actinomycetes of the genera Actinoplanes, Kineosporia and Cryptosporangium, which have quite common morphological characteristics, were frequently isolated from leaf-litter samples using the RC method. It is possible that these three genera acquired common properties during a process of convergent evolution. By contrast, strains belonging to the suborder Streptosporangineae were exclusively isolated from soils. A comparison of the sampling sites revealed no significant difference in taxonomic diversity between these sites. Among the non-streptomycetes, 156 strains (19%) were considered as new taxa distributed into 21 genera belonging to 12 families. Interestingly, the isolation of actinomycetes from leaf-litter samples using the RC method proved to be the most efficient way to isolate new actinomycetes in Vietnam, especially the Micromonosporaceae species.
TL;DR: One of the compounds displayed very good antibacterial activity in the presence of bovine surfactant, which interacts with daptomycin or A54145E to inhibit their antibacterial activities.
Abstract: A54145 is a complex of lipopeptide antibiotics produced by Streptomyces fradiae. A54145 factors are structurally related to daptomycin, with four modified amino acids, only one of which is present in daptomycin. We generated three mutants defective in lptJ, lptK or lptL, whose gene products are involved in the formation of hydroxy-Asn(3) (hAsn(3)) and methoxy-Asp(9) (moAsp(9)). Each of the mutants produced novel lipopeptides related to A54145 and the profiles allowed assignment of functions for those genes. We constructed strains carrying different combinations of these genes coupled with a mutation in the lptI gene involved in the biosynthesis of 3-methyl-Glu(12) (3mGlu(12)), and all recombinants produced novel lipopeptides. One of the compounds displayed very good antibacterial activity in the presence of bovine surfactant, which interacts with daptomycin or A54145E to inhibit their antibacterial activities.
TL;DR: Three new phthalide derivatives named 5-(3′-methyl-2′-butenyl)-2-hydroxy-3-methoxy-4-methylbenzoic acid, zinniol anhydride, and porriolide isolated from the liquid culture of the plant endophytic fungus Pestalotiopsis photiniae displayed significant antifungal activities against three plant pathogens.
Abstract: Three new phthalide derivatives (1-3) named 5-(3'-methyl-2'-butenyl)-2-hydroxy-3-methoxy-4-methylbenzoic acid (1), 5-(3'-carboxyl-3'-methyl-2E-allyloxy)-3-methoxy-4-methylphthalide (2) and 5-(3',3'-dimethylallyloxy)-2-methoxycarbonyl-3-methoxy-4-methylbenzoic acid (3) together with six known phthalide derivatives named 5-(3',3'-dimethylallyloxy)-3-methoxy-4-methylphthalide (4), zinnimidine (5), 5-(3',3'-dimethylallyloxy)-3-methoxy-4-methylphthalide (6), 5-(3',3'-dimethylallyloxy)-3-methoxy-4-methylphthalic acid (7), zinniol anhydride (8) and porriolide (9) were isolated from the liquid culture of the plant endophytic fungus Pestalotiopsis photiniae isolated from the Chinese Podocarpaceae plant Podocarpus macrophyllus. Their structures were elucidated by extensive spectroscopic analysis. Compounds 1-9 displayed significant antifungal activities against three plant pathogens.
TL;DR: This research presents a novel approach to drug discovery called “combinatorial biosynthesis and natural product drug discovery” that combines the efforts of two universities, University of Wisconsin and Yunnan University, to solve the problem of drug resistance in animals.
Abstract: isolation, structure determination and cytotoxicity of two new bafilomycins, 9-hydroxybafilomycin D (Ia) and 29-hydroxybafilomycin D (Ib), together with nine known bafilomycins