• Proceedings of the PSK Conference
• /
• 2003.10a
• /
• pp.85-87
• /
• 2003

$\beta$-Lactams are historically and clinically representative antibiotics used for therapeutic purposes. In early days, penicillin (penam antibiotic) and cephalosporin (cephem antibiotic) were found in culture broth of two different filamentous fungi, Penicillium chrysogenum and Acremonium chrysogenum. Since 1970, a variety of $\beta$-lactam structures have been discovered from bacterial cultures including Streptomyces species, which are known as cephamycin, cephabacin (cephem antibiotics), clavulanic acid (oxopenam antibiotic), thienamycin (carbapenem antibiotic), and sulfazecin (monobactam antibiotic). (omitted)

• Journal of Microbiology and Biotechnology
• /
• v.14 no.3
• /
• pp.635-638
• /
• 2004

An ATP-binding-cassette (ABC) transporter gene in the cephabacin biosynthetic gene cluster of Lysobacter lactamgenus was characterized. The amplified orf10 (cpbJ) gene was subcloned into pET-28a(+) vector and expressed in E. coli BL21(DE3) strain by 0.5 mM IPTG at $30^{\circ}C$. The membrane fraction of recombinant E. coli cells was separated by ultracentrifugation, and solubilized using 2.5% octyl-$\beta$-D-glucoside. Using the solubilized membrane fraction, the artificial proteoliposomes were reconstituted and analyzed for the biological activity of CpbJ protein. Upon measuring ATPase activity, the proteoliposome made from recombinant E. coli membrane proteins showed slightly higher activity than that from host E. coli membrane proteins. In the measurement of membrane transport activity, the reconstituted proteoliposome of recombinant E. coli membrane proteins exhibited higher activity when both substrates of cephalosporin C and L-Ala-L-Ser were applied, compared to the case of cephalosporin C or L-Ala-L-Ser only. It implies that the CpbJ protein is an ABC transporter secreting cephabacin antibiotics synthesized in cytoplasm.

• Archives of Pharmacal Research
• /
• v.15 no.3
• /
• pp.234-238
• /
• 1992

Using cell-free extract of Lysobacter lactamgenus, enzymatic conversion of $\delta$-L-($\alpha$-aminoadiphyl)-L-cysteinyl-D-valine (ACV) the first substrate of $\beta$-lactam biosynthesis, into antibiotic compounds was attempted. In high performance liquid chromatographic (HPLC) analysis, the biosynthetic intermediates for cephalosporin antibiotics including isopenicillin N, deacetoxycephalosporin C, deacetylcephalosporin C and unknown cephem compound were detected in reaction mixtures. It implies that cephabacin compounds from L lactamgenus could be produced by biosynthetic routes through penicillin ring formation and its expansion to cephalosporin ring, likely as cephalosporin C from Cephalosporium or cephamycin C from Streptomyces. Among biosynthetic enzyme in cell-free extract, the ring formation activity (isopenicillin N synthetase activity) was separated in 50-60% of ammonium sulfate fraction, and ring expansion activity (deacetoxycephalosporin C synthetase activity) was found to be in 40-50% fraction. The partially purified isopenicillin N synthetase could convert as much as 90% ACV to isopenicillin N during 6-hour reaction.

• Bulletin of the Korean Chemical Society
• /
• v.15 no.6
• /
• pp.453-455
• /
• 1994

Semiempirical MO calculations are applied to estimate the substituent effects on acylations of the nonfused N-vinyl-2-amino $\beta-lactams$ having frameworks analogous to 3-cephems. The stabilization energy for the reaction intermediate of the nucleophilic attack by the hydroxide ion is selected as the reactivity index and calculated by AM1 and PM3 methods for the model $\beta-lactams$ with substituents at the C1 and N-vinyl terminal positions. The reactivities are larger for -SH connected to the C1 and strong $\pi-acceptors$ at the N-vinyl terminal implying the large reactivity for known active cephalosporins. Quantum chemical calculation of stabilization energy could be useful in correlating antibiotic activities of many compounds obtained as derivatives of a lead compound.

• Applied Biological Chemistry
• /
• v.40 no.1
• /
• pp.23-29
• /
• 1997

To develop novel cephem antibiotics, We have synthesized a new compound, named YH-487, by attaching the thiol and aminothiazole residue to $C_3$ and $C_7$ position of 7-ACA, respectively. Several characteristics such as structure, antibiotic spectrum, action mechanism, stability against ${\beta}-lactamase$ and synergistic effect were investigated. Anti-bactericidal activity of YH-487 against gram-positive and gram-negative bacteria were superior to that of the other cephem antibiotics. We have examined the action mechanisms of YH-487 using penicillin binding protein (PBP) assay, and found that the bactericidal activity was obtained by inhibiting PBP-1A, PBP-1B and PBP-3. YH-487 showed synergistic effect with gentamicin, tobramycin, and amikacin against Pseudomonas aeruginosa. In addition, YH-487 was effective against Enterobacter cloacae in combination with amikacin. Based on the above observations, YH-487 was classified as a novel third-generation ${\beta}-lactam$ antibiotics.

• Journal of The Korean Society of Clinical Toxicology
• /
• v.4 no.1
• /
• pp.65-68
• /
• 2006

Contact urticaria describes a wheal and falre response elicitied within 30-60 minutes after cutaneous exposure to certain agents. Contact urticaria encompasses a number of different clinical manifestations and the symptoms which can vary from the mildest forms of burning, stinging and itching sensation to life-threatening anaphylaxis referred to as contact urticaria syndrome. Cefotiam is one of the most popular second generation cephem antibiotic used in korea. Since 1975, contact urticaria due to cephalosporins has been reported, and also, in japan, this reported from about last 15 years. Recently we experienced three nurses working at the general wards with showing contact urticaria and anaphylaxis after occupational exposure to cefotiam antibiotics.

• Journal of Microbiology and Biotechnology
• /
• v.11 no.1
• /
• pp.153-159
• /
• 2001

In order to clone the peptide synthetase gene form Lysobacter lactamgenus IFO 14,288, the gene fragments were amplified using primers for the adenylation domain and the thionylation domain of the peptide synthetase genes in other organisms by polymerase chain reaction (PCR). The resulting 0.5-kb fragment was cloned in a pGEM-T vector, and the nucleotide sequences were determined. Six different PCR products were obtained; three were identified to be a part of L-$\alpha$-aminoadipyl-L-cysteinyl-D-valine (ACV) synthetase and three to be other peptide synthetases. Using each of the two different classes of PCR products as mixed probes, a cosmid library of L. lactamgenus chromosomal DNA constructed in a pHC79 vector was screened by an in situ hybridization procedure, and one positive clone was selected which was bound by peptide synthetase gene fragments as well as ACV synthetase gene fragments. The partial sequence analysis formt he obtained pPTS-5 cosmid showed th presence of more than two open reading frames. These were for two putative membrane transporters, which were homologous with several integral membrane proteins including the ABC transporter ATP-binding protein of E. coli (YbjZ) and the metal ion uptake protein of Bacillus subtilis (YvrN). A 45% homology was also found between the two transporter proteins at the carboxy terminus. Through a hydropathy analysis and transmembrane analysis. 4-5 transmembrane domains were found in these two proteins. When the genes were expressed in Escherichia coli, the gene products inhibited the hose cell growth, probably due to the disturbance of the membrane transport system.

• Korean Journal of Clinical Pharmacy
• /
• v.22 no.1
• /
• pp.9-12
• /
• 2012

Background: Cefcapene pivoxil hydrochloride, is an ester-type oral cephem antibiotic. This study was performed to compare the pharmacokinetics and evaluate the bioequivalence of two cefcapene pivoxil hydrochloride 75 mg formulations. Method: In a randomized $2{\times}2$ crossover study, sixty healthy male volunteers were randomly assigned into two groups. After a single dose of 75 mg cefcapene pivoxil hydrochloride oral administration, blood samples were collected at specific time intervals from 0-12 hours. The plasma concentrations of cefcapene pivoxil hydrochloride were determined by LC-MS/MS. The pharmacokinetic parameters were determined from the plasma concentration-time profiles of both formulations. The pharmacokinetic parameters such as $AUC_{last}$, $AUC_{inf}$ and $C_{max}$, were calculated and the 90% confidence intervals for test/reference ratio for pharmacokinetic parameters were obtained by analysis of variance on logarithmically transformed data. Results: The mean value for $AUC_{last}$ in test and reference drug was $4053.1{\pm}876.5\;ng{\cdot}hr/mL$ and $3595.7{\pm}1029.1\;ng{\cdot}h/mL$, respectively. The mean value for $C_{max}$ in test and reference drug was $1324.9{\pm}321.4$ ng/mL and $1159.1{\pm}335.9$ ng/mL, respectively. The 90% confidence intervals of the $AUC_{last}$ and $C_{max}$ ratio for test drug and reference drug were log 1.09-log1.22 and log 1.09-log1.24, respectively. No adverse events were reported by subjects or found on analysis of vital signs or laboratory tests. Conclusion: This single dose study found that the test and reference products met the regulatory criteria for bioequivalence in these health volunteers. Both formulations were safe and well tolerated in 75 mg of cefcapene pivoxil hydrochloride.