TY - JOUR
T1 - Biosynthetic concepts for the production of beta-lactam antibiotics in Penicillium chrysogenum
AU - Weber, Stefan S.
AU - Bovenberg, Roel A. L.
AU - Driessen, Arnold J. M.
PY - 2012/2
Y1 - 2012/2
N2 - Industrial production of beta-lactam antibiotics by the filamentous fungus Penicillium chrysogenum is based on successive classical strain improvement cycles. This review summarizes our current knowledge on the results of this classical strain improvement process, and discusses avenues to improve beta-lactam biosynthesis and to exploit P. chrysogenum as an industrial host for the production of other antibiotics and peptide products. Genomic and transcriptional analysis of strain lineages has led to the identification of several important alterations in high-yielding strains, including the amplification of the penicillin biosynthetic gene cluster, elevated transcription of genes involved in biosynthesis of penicillin and amino acid precursors, and genes encoding microbody proliferation factors. In recent years, successful metabolic engineering and synthetic biology approaches have resulted in the redirection of the penicillin pathway towards the production of cephalosporins. This sets a new direction in industrial antibiotics productions towards more sustainable methods for the fermentative production of unnatural antibiotics and related compounds.
AB - Industrial production of beta-lactam antibiotics by the filamentous fungus Penicillium chrysogenum is based on successive classical strain improvement cycles. This review summarizes our current knowledge on the results of this classical strain improvement process, and discusses avenues to improve beta-lactam biosynthesis and to exploit P. chrysogenum as an industrial host for the production of other antibiotics and peptide products. Genomic and transcriptional analysis of strain lineages has led to the identification of several important alterations in high-yielding strains, including the amplification of the penicillin biosynthetic gene cluster, elevated transcription of genes involved in biosynthesis of penicillin and amino acid precursors, and genes encoding microbody proliferation factors. In recent years, successful metabolic engineering and synthetic biology approaches have resulted in the redirection of the penicillin pathway towards the production of cephalosporins. This sets a new direction in industrial antibiotics productions towards more sustainable methods for the fermentative production of unnatural antibiotics and related compounds.
KW - beta-Lactam
KW - Metabolic engineering
KW - Penicillium chrysogenum
KW - Synthetic biology
KW - ISOPENICILLIN N-ACYLTRANSFERASE
KW - CEPHALOSPORIN-C BIOSYNTHESIS
KW - AMINOADIPYL-CYSTEINYL-VALINE
KW - ACREMONIUM-CHRYSOGENUM
KW - ASPERGILLUS-NIDULANS
KW - PHENYLACETIC ACID
KW - GENE-CLUSTER
KW - STREPTOMYCES-CLAVULIGERUS
KW - SACCHAROMYCES-CEREVISIAE
KW - MULTIDRUG-RESISTANCE
U2 - 10.1002/biot.201100065
DO - 10.1002/biot.201100065
M3 - Review article
SN - 1860-6768
VL - 7
SP - 225
EP - 236
JO - Biotechnology Journal
JF - Biotechnology Journal
IS - 2
ER -