真菌β-内酰胺次级代谢调控的分子机制

Molecular mechanism of secondary metabolism regulatory of β-lactam biosynthesis in fungi

真菌中青霉素和头孢菌素生物合成起始于共同前体，异青霉素Ｎ是这两合成途径的分叉中间体；经各自合成途径分别转化为青霉素和头孢菌素。在转录及转录后水平上，β内酰胺生物合成基因表达受多种顺式作用元件与反式作用因子以及营养源等多方面的调控。

The most commonly used β-lactam antibiotics for the therapy of infectious diseases are penicillin and cephalosporin. The biosynthetic pathways of penicillin in Penicillium chrysogenum and cephalosporin in Cophalosporium acremonium have the first two steps in common. Both antibiotics are formed by condensation of the three precursor amino acids (L-α-aminoadipic acid, L- cysteine and L-valine) to form the δ- (L-α-aminoadipyl) -L-cysteinyl-D -valine tripeptide (ACV ). Penicillin biosynthesis is catalyzed by three enzymes encoded by acvA(pcbAB), ipnA(pcbC), and aatA(penDE). The genes are organized into a cluster in C.acremonium, in addition to acvA and ipnA, a second cluster contains the genes encoding enzymes that catalyze the reactions of the later steps of the caphalosporin pathway(cefEF and cefG). So far, it was identified that expression of the fungal β-lactam biosynthesis genes airs controlled by the eis-acting elements and trans-acting factors in transcriptional regulation and by the C-source in post transcriptional regulation. The elucidation of several regulatory mechanisms have contributed to rational strain improvement programs. The knowledge of biosynthesis genes has already been used to produce new compounds.