They include the penicillins and many of the cephalosporins."

Eighteen alkaloids (seven aporphine and 11 phenanthrenes)were semisynthesized from boldine and used to test inhibition both ofTopA activity and of cell growth.

They include the penicillins and many of the cephalosporins.

Micah J. Bodner, Rongfeng Li, Ryan M. Phelan, , Kristos A. Moshos, Evan P. Lloyd, Craig A. Townsend

DANS is an institute of KNAW and NWO

Expression of the cephalosporin biosynthesis genes in A. chrysogenum is controlled by several global regulators including the carbon catabolite repressor CreA (), the pH regulator PacC () and the winged helix transcriptional factor CPCR1 ().

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T1 - Definition of the common and divergent steps in carbapenem β-lactam antibiotic biosynthesis

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Taken together, these data show that in a wild-type strain of A. nidulans, expression of biosynthesis genes, at least of the acvA gene, is rate limiting. It remains to be elucidated, however, whether this holds for penicillin and cephalosporin production strains. Nevertheless, the expression level of biosynthesis genes, as shown for the cephalosporin C production, is of great importance.

The mechanism by which LTscatalyse the fragmentation is unique.

Skatrud et al. () reported a 15% increase in cephalosporin C production in an industrial strain of A. chrysogenum (394-4) by transformation of the strain with an extra copy of the DAOC synthetase/DAC hydroxylase gene (cefEF) (to give strain LU4-97-6) (Fig. ). However, when the experiments were carried out, it was not known that cefG encoding acetyl-CoA:DAC acetyltransferase is closely linked to cefEF (Fig. ) and was also present on the plasmid used for transformation. Then it was demonstrated that transformants of wild-type A. chrysogenum, carrying additional copies of the cefG gene only, showed a direct relationship between cefG copy number, cefG mRNA levels, and cephalosporin C titers, suggesting that this enzyme might be a rate-limiting step in cephalosporin C production (, ). Hence, the effect of the cefEF gene alone in increasing cephalosporin C production remains unclear.

T1 - Biochemical pathways supporting beta-lactam biosynthesis in the springtail Folsomia candida

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3. Jang TN, Wang FD, Wang LS, Liu CY, Liu IM. Xanthomonas maltophilia bacteremia: an analysis of 32 cases. J Formosan Med Assoc 1992; 91:1170-1176.

During homeostasis, includinggrowth, cell wall is simultaneously biosynthesized and degraded.

The Gram-positivepathogen uses one primary resistance mechanism.

Although the presence in P. chrysogenum Wis54-1255 of a transport system for the side chain precursor phenylacetic acid was reported (), subsequent investigations showed that phenylacetic acid passes the plasma membrane via passive diffusion of the protonated species ().

The mechanism involves a histidine asacid/base catalyst, which is unique for glycosidases.

Recommended dosages for specific agents are given in .

Cloned β-lactam biosynthesis genes can already be used for rational improvement of β-lactam production. DAOC and cephalosporin C can be enzymatically deacylated to form 7-aminodeacetoxycephalosporanic acid (7-ADCA) and 7-aminocephalosporanic acid (7-ACA), respectively; these are important intermediates in the manufacturing of oral cephalosporin antibiotics (Fig. ). Medically important oral cephalosporins, e.g., cephalexin and cephradine, are synthesized by derivatizing the 7-amino group of 7-ADCA or 7-ACA with appropriate side chain moieties (). Although cephalosporins are superior antibiotics compared to penicillins, their production is limited because the process for producing 7-ADCA and 7-ACA is complex. Removal of the natural -α-aminoadipyl side chain from cephalosporins is inefficient (, ). Hence, there have been efforts in both directions: isolation of superior enzymes to remove the side chain directly and development of alternative biosynthetic routes to 7-ACA and/or 7-ADCA (, ).