• Title/Summary/Keyword: macrolactin A

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Structure Determination of Macrolactin Compounds with Antibacterial Activities Isolated from Bacillus polyfermenticus KJS-2 (Bacillus polyfermenticus KJS-2에서 분리된 항생물질 마크로락틴류의 구조결정)

  • Kim, Dong-Hee;Kang, Kyung-Ran;Kim, Hyun-Woo;Yoon, Si-Yeol;Kim, Chun-Gyu;Yamaguchi, Tokutaro;Sohng, Jae-Kyung;Kang, Jae-Seon
    • Journal of Life Science
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    • v.20 no.12
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    • pp.1792-1800
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    • 2010
  • In this study, we isolated five macrolactin compounds from a fermentation broth of Bacillus polyfermenticus KJS-2. The macrolactin compounds were structurally identified as macrolactin A (MA), 7-O-malonyl macrolactin A (MMA), 7-O-succinyl macrolactin A (SMA), macrolactin E (ME) and macrolactin F (MF) via a variety of NMR techniques, COZY, DEPT, HMQC and HMBC, and mass and specific rotation assays. The three macrolactin compounds, MA, MMA and SMA, profoundly inhibited the growth of both vancomycin-resistant Enterococci (VREs) and methicillin-resistant Staphylococcus aureus (MRSA), the inhibition of which were estimated via a disc agar diffusion bioassay. MA, MMA, and SMA exhibited antibacterial activities superior to those of vancomycin and teicoplanin.

Neuronal Cell Protection Activity of Macrolactin A Produced by Actinomadura sp.

  • Kim, Hyeon-Ho;Kim, Won-Gon;Ryoo, In-Ja;Kim, Chang-Jin;Suk, Jae-Eun;Han, Kyou-Hoon;Hwang, Se-Young;Yoo, Ick-Dong
    • Journal of Microbiology and Biotechnology
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    • v.7 no.6
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    • pp.429-434
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    • 1997
  • Macrolactin A, 24-membered macrolide, was isolated from the culture broth of Actinomadura sp. as a neuronal cell protecting substance. In the cell assay, this compound inhibited glutamate toxicity in N18-RE-105 cells with an $EC_50$ value of 0.5 ${\mu}g/ml.

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Isolation and Characterization of Antimicrobial Substance Macrolactin A Produced from Bacillus amyloliquefaciens CHO104 Isolated from Soil

  • Lee, Seung-Je;Cho, Jeong-Yong;Cho, Jung-Il;Moon, Jae-Hak;Park, Ki-Deok;Lee, Young-Ju;Park, Keun-Hyung
    • Journal of Microbiology and Biotechnology
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    • v.14 no.3
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    • pp.525-531
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    • 2004
  • A strain antagonistic to Fusarium solani, CHO104, was selected from approximately 100 microorganisms isolated from soil. Strain CHO104 was identified as Bacillus amyloliquefaciens and found to be Gram-positive based on the Biolog system and 16S rRNA methods. A culture broth of B. amyloliquefaciens CHO104 also exhibited antimicrobial activity against various microorganisms. As such, the EtOAc extract of the culture broth was isolated by various column chromatographic procedures and HPLC. The antimicrobial and antifungal substance was then characterized as macrolactin A $(C_{24}H_{34}O_5)$ using high-resolution EI-MS and NMR analyses, and found to be very effective in inhibiting the growth of Staphylococcus aureus, E. coli, and Botrytis cinerea, even when using a concentration of one-twentieth of the benzoic acid as the control compound.

Calculation of a First-In-Man Dose of 7-O-Succinyl Macrolactin A Based on Allometric Scaling of Data from Mice, Rats, and Dogs

  • Noh, Keumhan;Kang, Wonku
    • Biomolecules & Therapeutics
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    • v.25 no.6
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    • pp.648-658
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    • 2017
  • 7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.

Exploration of the Glycosyltransferase BmmGT1 from a Marine-Derived Bacillus Strain as a Potential Enzyme Tool for Compound Glycol-Diversification

  • Liu, Quanquan;Ren, Pengfei;Liu, Yang;Qin, Wen;Li, Huayue;Li, Wenli
    • Journal of Microbiology and Biotechnology
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    • v.28 no.6
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    • pp.931-937
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    • 2018
  • Glycosyltransferases (GTs) from microbes are an emerging and rich source for efficient glycol-transformation of natural/unnatural compounds. Here, we probed the catalytic capability and substrate promiscuity of BmmGT1 from marine-derived Bacillus methylotrophicus B-9987. The regioselectivity of BmmGT1 on macrolactin A (1) was explored by optimization of the reaction conditions, in which a series of O-glycosylated macrolactins (1a-1e) were generated, including two new di/tri-O-glucosyl analogs (1b and 1e). Furthermore, BmmGT1 was able to catalyze the glycosylation of the thiol (S-) or amine (N-) sites of phenolic compounds (2 and 3), leading to the generation of N- (2a) or S-glycosides (3a and 3b). The present study demonstrates that BmmGT1 could serve as a potential enzyme tool for O-, N-, or S-glycosyl structural diversification of compounds for drug discovery.

The Preventive Effect of Bacillus polyfermenticus KJS-2 and Bacillus mojavensis KJS-3 on Triton WR-1339-induced Hyperlipidemia (Triton WR-1339로 유도된 고지혈증에 대한 Bacillus polyfermenticus KJS-2와 Bacillus mojavensis KJS-3의 예방효과)

  • Lee, Jin Young;Lee, Seung Jae;Kim, Hyung Hoi;Kang, Jae Seon
    • Journal of Life Science
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    • v.31 no.3
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    • pp.346-355
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    • 2021
  • The purpose of this study was to evaluate the possibility that administration of Bacillus polyfermenticus KJS-2 (BP2), Bacillus mojavensis KJS-3 (Moja3), and their mixtures could control serum lipid levels. We observed changes in the blood cell level, metabolic function evaluation, and blood lipid levels after two weeks of oral administration of these microbial strains to hyperlipidemia-induced rats. Measurements of major cell changes in the white blood cells (WBC) indicated no significant effects due to the administration of the microbial strains. Platelet (PLT) levels decreased by 18.4% in the Triton WR-1339-treated group (NCON) and recovered to the control (CON) group levels in the positive control (PCON) group and the microbial strain-administered groups (p<0.05). No functional changes were observed in red blood cells (RBC) by Triton WR-1339-induced hyperlipidemia. The blood AST, ALT, BUN, and creatinine levels did not indicated effects on liver and kidney function, and all rats administered the microbial mixture recovered. The blood lipid levels in the microbe-treated groups indicated reduced levels of triglyceride (TG) and total cholesterol (TC), and increased levels of serum HDL cholesterol. The HMG-CoA inhibition rate of 7-O-succinyl macrolactin A (SMA) produced by BP2 showed similar activity at a concentration of 1,000 times lower than that achieved with atorvastatin. The administration of the microbial strains to the Triton WR-1339-induced rat model of hyperlipidemia resulted in reduced weight gain without affecting the food and water intake. Thus, blood circulation can be improved by controlling serum lipid levels by the combined administration of the BP2 and Moja3 microbial strains.

Brief Introduction of Research Progresses in Control and Biocontrol of Clubroot Disease in China

  • He, Yueqiu;Wu, Yixin;He, Pengfei;Li, Xinyu
    • 한국균학회소식:학술대회논문집
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    • 2015.05a
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    • pp.45-46
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    • 2015
  • Clubroot disease of crucifers has occurred since 1957. It has spread to the whole China, especially in the southwest and nourtheast where it causes 30-80% loss in some fields. The disease has being expanded in the recent years as seeds are imported and the floating seedling system practices. For its effective control, the Ministry of Agriculture of China set up a program in 2010 and a research team led by Dr. Yueqiu HE, Yunnan Agricultural University. The team includes 20 main reseachers of 11 universities and 5 institutions. After 5 years, the team has made a lot of progresses in disease occurrence regulation, resources collection, resistance identification and breeding, biological agent exploration, formulation, chemicals evaluation, and control strategy. About 1200 collections of local and commercial crucifers were identified in the field and by artificiall inoculation in the laboratories, 10 resistant cultivars were breeded including 7 Chinese cabbages and 3 cabbages. More than 800 antagostic strains were isolated including bacteria, stretomyces and fungi. Around 100 chemicals were evaluated in the field and greenhouse based on its control effect, among them, 6 showed high control effect, especially fluazinam and cyazofamid could control about 80% the disease. However, fluzinam has negative effect on soil microbes. Clubroot disease could not be controlled by bioagents and chemicals once when the pathogen Plasmodiophora brassicae infected its hosts and set up the parasitic relationship. We found the earlier the pathogent infected its host, the severer the disease was. Therefore, early control was the most effective. For Chinese cabbage, all controlling measures should be taken in the early 30 days because the new infection could not cause severe symptom after 30 days of seeding. For example, a biocontrol agent, Bacillus subtilis Strain XF-1 could control the disease 70%-85% averagely when it mixed with seedling substrate and was drenching 3 times after transplanting, i.e. immediately, 7 days, 14 days. XF-1 has been deeply researched in control mechanisms, its genome, and development and application of biocontrol formulate. It could produce antagonistic protein, enzyme, antibiotics and IAA, which promoted rhizogenesis and growth. Its The genome was sequenced by Illumina/Solexa Genome Analyzer to assembled into 20 scaffolds then the gaps between scaffolds were filled by long fragment PCR amplification to obtain complet genmone with 4,061,186 bp in size. The whole genome was found to have 43.8% GC, 108 tandem repeats with an average of 2.65 copies and 84 transposons. The CDSs were predicted as 3,853 in which 112 CDSs were predicted to secondary metabolite biosynthesis, transport and catabolism. Among those, five NRPS/PKS giant gene clusters being responsible for the biosynthesis of polyketide (pksABCDEFHJLMNRS in size 72.9 kb), surfactin(srfABCD, 26.148 kb, bacilysin(bacABCDE 5.903 kb), bacillibactin(dhbABCEF, 11.774 kb) and fengycin(ppsABCDE, 37.799 kb) have high homolgous to fuction confirmed biosynthesis gene in other strain. Moreover, there are many of key regulatory genes for secondary metabolites from XF-1, such as comABPQKX Z, degQ, sfp, yczE, degU, ycxABCD and ywfG. were also predicted. Therefore, XF-1 has potential of biosynthesis for secondary metabolites surfactin, fengycin, bacillibactin, bacilysin and Bacillaene. Thirty two compounds were detected from cell extracts of XF-1 by MALDI-TOF-MS, including one Macrolactin (m/z 441.06), two fusaricidin (m/z 850.493 and 968.515), one circulocin (m/z 852.509), nine surfactin (m/z 1044.656~1102.652), five iturin (m/z 1096.631~1150.57) and forty fengycin (m/z 1449.79~1543.805). The top three compositions types (contening 56.67% of total extract) are surfactin, iturin and fengycin, in which the most abundant is the surfactin type composition 30.37% of total extract and in second place is the fengycin with 23.28% content with rich diversity of chemical structure, and the smallest one is the iturin with 3.02% content. Moreover, the same main compositions were detected in Bacillus sp.355 which is also a good effects biocontol bacterial for controlling the clubroot of crucifer. Wherefore those compounds surfactin, iturin and fengycin maybe the main active compositions of XF-1 against P. brassicae. Twenty one fengycin type compounds were evaluate by LC-ESI-MS/MS with antifungal activities, including fengycin A $C_{16{\sim}C19}$, fengycin B $C_{14{\sim}C17}$, fengycin C $C_{15{\sim}C18}$, fengycin D $C_{15{\sim}C18}$ and fengycin S $C_{15{\sim}C18}$. Furthermore, one novel compound was identified as Dehydroxyfengycin $C_{17}$ according its MS, 1D and 2D NMR spectral data, which molecular weight is 1488.8480 Da and formula $C_{75}H_{116}N_{12}O_{19}$. The fengycin type compounds (FTCPs $250{\mu}g/mL$) were used to treat the resting spores of P. brassicae ($10^7/mL$) by detecting leakage of the cytoplasm components and cell destruction. After 12 h treatment, the absorbencies at 260 nm (A260) and at 280 nm (A280) increased gradually to approaching the maximum of absorbance, accompanying the collapse of P. brassicae resting spores, and nearly no complete cells were observed at 24 h treatment. The results suggested that the cells could be lyzed by the FTCPs of XF-1, and the diversity of FTCPs was mainly attributed to a mechanism of clubroot disease biocontrol. In the five selected medium MOLP, PSA, LB, Landy and LD, the most suitable for growth of strain medium is MOLP, and the least for strains longevity is the Landy sucrose medium. However, the lipopeptide highest yield is in Landy sucrose medium. The lipopeptides in five medium were analyzed with HPLC, and the results showed that lipopeptides component were same, while their contents from B. subtilis XF-1 fermented in five medium were different. We found that it is the lipopeptides content but ingredients of XF-1 could be impacted by medium and lacking of nutrition seems promoting lipopeptides secretion from XF-1. The volatile components with inhibition fungal Cylindrocarpon spp. activity which were collect in sealed vesel were detected with metheds of HS-SPME-GC-MS in eight biocontrol Bacillus species and four positive mutant strains of XF-1 mutagenized with chemical mutagens, respectively. They have same main volatile components including pyrazine, aldehydes, oxazolidinone and sulfide which are composed of 91.62% in XF-1, in which, the most abundant is the pyrazine type composition with 47.03%, and in second place is the aldehydes with 23.84%, and the third place is oxazolidinone with 15.68%, and the smallest ones is the sulfide with 5.07%.

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