Regulation and compartmentalization of β-lactam biosynthesis.
Bottom Line: Similarly, the Acremonium two-component CefD1-CefD2 epimerization system is also located in microbodies.This compartmentalization implies intracellular transport of isopenicillin N (in the penicillin pathway) or isopenicillin N and penicillin N in the cephalosporin route.Two transporters of the MFS family cefT and cefM are involved in transport of intermediates and/or secretion of cephalosporins.
Affiliation: Institute of Biotechnology of León, Science Park, Avda. Real 1, 24006 León, Spain. firstname.lastname@example.orgShow MeSH
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Mentions: Two early enzymatic steps are common to all the classical β‐lactam producers, resulting in the formation of isopenicillin N (IPN), the first compound in the pathway with antibiotic activity. The first enzyme of the pathway is the ACV synthetase (ACVS), a non‐ribosomal peptide synthetase. The ACV synthetases are very large multifunctional proteins (Mr in the order of 420 kDa) encoded by intron‐free genes of 11 kb named pcbAB (Díez et al., 1990; Gutiérrez et al., 1991) which occur in the fungal and bacterial penicillin and cephalosporin (and cephamycin) clusters (Fig. 3). This enzyme sequentially activates the three substrates with ATP to form aminoacyl‐adenylates, binds them to the enzyme as thioesters, epimerizes the l‐valine to d‐valine, links together the three amino acids to form the peptide l‐δ(α‐aminoadipyl)‐l‐cysteinyl‐d‐valine (hereafter named ACV) and, finally, releases this tripeptide from the enzyme by the action of an internal thioesterase activity. The ACV synthetases have three well conserved domains that activate each of the three amino acids respectively (Zhang and Demain, 1992; Aharonowitz et al., 1993; Martín, 2000a).
Affiliation: Institute of Biotechnology of León, Science Park, Avda. Real 1, 24006 León, Spain. email@example.com