Cephalosporin C

The industrial production of higher-generation semisynthetic cephalosporins starts from 7-aminocephalosporanic acid (7-ACA), which is obtained by deacylation of the naturally occurring antibiotic cephalosporin C (CephC). The enzymatic process in which CephC is directly converted into 7-ACA by a cephalosporin C acylase has attracted industrial interest because of the prospects of simplifying the process and reducing costs. We recently enhanced the catalytic efficiency on CephC of a glutaryl acylase from Pseudomonas N176 (named VAC) by a protein engineering approach and solved the crystal structures of wild-type VAC and the H57βS-H70βS VAC double variant. In the present work, experimental measurements on several CephC derivatives and six VAC variants were carried out, and the binding of ligands into the VAC active site was investigated at an atomistic level by means of molecular docking and molecular dynamics simulations and analyzed on the basis of the molecular geometry of encounter complex formation and protein-ligand potential of mean force profiles.

Composting is a potential alternative for cephalosporin C fermentation dregs (CCFDs) compared with incineration process or landfill because of its advantage of recovering nutrients. In this research, CCFDs and activated sludge (AS) were co-composted to analyze the feasibility of recycling the nutrients in CCFDs. A pilot-scale aerobic composting system with an auto-control system was used in this research, and the maturity and security of the compost product were evaluated. The temperature of the composting mixtures was maintained above 55°C for more than 3 days during the composting, indicating that co-composting of CCFDs and AS could reach the compost maturity standard, and the seeds germination index (GI) increased from 17.61% to 68.93% by the end of the composting process (28 days). However, the degradation rate of cephalosporin C (CPC) was only 6.58% during the composting process. Monitoring the quality of antibiotic resistance genes (ARGs) in the composts showed that the log copy of blaTEM in the composts increased from 2.

Cephalosporin C (CPC) productivity of Acremonium chrysogenum has been improved significantly through classical strain improvement programs. Here, we used transcription and metabolite profiling to address mechanisms underlying CPC production in a high yield (HY) strain. Transcription and metabolite profiling indicated that enzymes involved in amino acid production are higher in abundance in the HY strain. Moreover, results indicate a higher flow of precursors from the glycolysis and gluconeogenesis pathways to serine synthesis at the late stage of fermentation in the HY strain. In addition, less pyruvate would enter the TCA cycle thus favoring valine synthesis. Amino acid production would also benefit from a more active pentose phosphate pathway and γ-amino butyric acid shunt both generating NADPH. Moreover the glyoxylate pathway seems to be more active in the HY strain. These results may provide new leads for CPC strain improvement in industry.

in English, RussianSintetaza tsefalosporinov-kislot (cephalosporin-acid synthetase, CASA) spetsifichna k sintezu tsefalosporinov-kislot; produktsiia étogo fermenta v kletkakh Escherichia coli soprovozhdaetsia nakopleniem neprotsessirovannogo nerastvorimogo predshestvennika. Dlia optimizatsii usloviĭ produktsii rekombinantnoĭ CASA izuchali éffekty takikh parametrov kul'tivirovaniia shtamma-produtsenta kak sostav pitatel'noĭ sredy, posevnaia doza, temperatura kul'tivirovaniia. Dlia sovershenstvovaniia vektora ékspressii CASA byli sozdany dopolnitel'nye konstruktsii dlia produktsii varianta CASA s signal'noĭ posledovatel'nost'iu L-asparaginazy Erwinia carotovora (ansCASA) i “bezlidernogo” varianta CASA. Udalenie N-kontsevoĭ signal'noĭ posledovatel'nosti na poriadok snizhalo uroven' produktsii funktsional'no aktivnoĭ CASA i podavlialo rost shtamma. Vvedenie signal'noĭ posledovatel'nosti L-asparaginazy povyshalo udel'nuiu aktivnost' fermenta v poluchennom shtamme.