Cephalosporin C Zinc Salt

Cephalosporins are currently the most widely used antibiotics in clinical practice. The main strain used for the industrial production cephalosporin C (CPC) is Acremonium chrysogenum. CPC has the advantages of possessing a broad antibacterial spectrum and strong antibacterial activity. However, the yield and titer of cephalosporins obtained from A. chrysogenum are much lower than penicillin, which is also a β-lactam antibiotic produced by Penicillium chrysogenum. Molecular biology research into A. chrysogenum has focused on gene editing technologies, multi-omics research which has provided information on the differences between high- and low-yield strains, and metabolic engineering involving different functional genetic modifications and hierarchical network regulation to understand strain characteristics. Furthermore, optimization of the fermentation process is also reviewed as it provides the optimal environment to realize the full potential of strains. Combining rational design to control the metabolic network, high-throughput screening to improve the efficiency of obtaining high-performance strains, and real-time detection and controlling in the fermentation process will become the focus of future research in A. chrysogenum. This minireview provides a holistic and in-depth analysis of high-yield mechanisms and improves our understanding of the industrial value of A. chrysogenum. KEY POINTS: · Review of the advances in A. chrysogenum characteristics improvement and process optimization · Elucidate the molecular bases of the mechanisms that control cephalosporin C biosynthesis and gene expression in A. chrysogenum · The future development trend of A. chrysogenum to meet industrial needs.

d-amino acid oxidase (DAAO, EC 1.4.3.3) is used in many biotechnological processes. The main industrial application of DAAO is biocatalytic production of 7-aminocephalosporanic acid from cephalosporinCwith a two enzymes system. DAAO from the yeastTrigonopsis variabilis(TvDAAO) shows the best catalytic parameters with cephalosporinCamong all known DAAOs. We prepared and characterized multipoint TvDAAO mutants to improve their activity towards cephalosporinCand increase stability. All TvDAAO mutants showed better properties in comparison with the wild-type enzyme. The best mutant was TvDAAO with amino acid changes E32R/F33D/F54S/C108F/M156L/C298N. Compared to wild-type TvDAAO, the mutant enzyme exhibits a 4 times higher catalytic constant for cephalosporinCoxidation and 8- and 20-fold better stability against hydrogen peroxide inactivation and thermal denaturation, respectively. This makes this mutant promising for use in biotechnology. The paper also presents the comparison of TvDAAO catalytic properties with cephalosporinCreported by others.

More than 40 years ago, it was reported that methionine markedly stimulated production of cephalosporin C by Cephalosporium acremonium. Over the years, many hypotheses were put forth to explain this phenomenon. The accumulating evidence strongly supported the concept that methionine stimulates by inducing enzymes of the biosynthetic pathway such as delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase, isopenicillin N synthase, and deacetoxycephalosporin C synthase. This mechanism has been strengthened by the finding that transcription of the genes encoding the above enzymes is markedly enhanced by growth with methionine. An effect of methionine in the fermentation unrelated to the titer stimulation is its contribution of the sulfur atom to the cephalosporin molecule. Methionine also stimulates mycelial fragmentation; the relationship between this effect on hyphal differentiation and the induction of the cephalosporin synthases remains to be elucidated.