Molecular Regulation of b-Lactam Biosynthesis in Filamentous Fungi
نویسنده
چکیده
INTRODUCTION .......................................................................................................................................................547 GENERAL ASPECTS OF b-LACTAM COMPOUNDS........................................................................................548 BIOSYNTHESIS OF PENICILLINS AND CEPHALOSPORINS: AN OUTLINE............................................549 GENETIC NOMENCLATURE .................................................................................................................................549 CLUSTERING OF BIOSYNTHESIS GENES ........................................................................................................550 STRUCTURAL GENES AND DEDUCED PROTEINS ........................................................................................550 Genes Common to Penicillinand Cephalosporin-Producing Fungi ..............................................................550 acvA (pcbAB), encoding ACVS...........................................................................................................................550 ipnA (pcbC), encoding IPNS ..............................................................................................................................553 Gene Specific for Penicillin Biosynthesis ............................................................................................................555 aatA (penDE), encoding IAT..............................................................................................................................555 Genes Specific for Cephalosporin Biosynthesis..................................................................................................556 cefD, encoding IPN epimerase...........................................................................................................................556 cefEF, encoding DAOC synthetase (ring expandase)/DAC hydroxylase .....................................................556 Gene Specific for Cephalosporin C Biosynthesis in Fungi ...............................................................................556 cefG, encoding acetyl-CoA:DAC acetyltransferase..........................................................................................556 COMPARTMENTALIZATION OF GENE PRODUCTS ......................................................................................557 ORIGIN OF b-LACTAM BIOSYNTHESIS GENES IN FUNGI .........................................................................557 REGULATORY CIRCUITS AND REGULATORY GENES .................................................................................558 Expression of Biosynthesis Genes under Standard Fermentation Conditions ..............................................558 Promoter Structures of the A. nidulans Genes acvA and ipnA .........................................................................559 Carbon Source Regulation.....................................................................................................................................560 pH Regulation Mediated by the Transcriptional Factor PACC.......................................................................561 Nitrogen Regulation ...............................................................................................................................................563 Amino Acids as Precursors and Mediators of Regulation................................................................................564 Influence of Phosphate and Oxygen.....................................................................................................................568 The CCAAT Box Binding Protein Complex PENR1..........................................................................................568 trans-Acting Mutations Affecting the Expression of Penicillin Biosynthesis Genes ......................................570 Posttranscriptional Regulation .............................................................................................................................571 REGULATION OF b-LACTAM BIOSYNTHESIS IN FUNGAL PRODUCTION STRAINS..........................571 APPLICATIONS .........................................................................................................................................................573 Increase of Expression of b-Lactam Biosynthesis Genes .................................................................................574 Genetic Engineering of b-LACTAM BIOSYNTHETIC PATHWAYS..............................................................574 Generation of Novel Compounds by Genetic Engineering of Peptide Synthetases.......................................575 CONCLUSIONS AND FUTURE DIRECTIONS....................................................................................................575 ACKNOWLEDGMENTS ...........................................................................................................................................578 REFERENCES ............................................................................................................................................................578
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