Abstract：
:Industrial production of semi-synthetic cephalosporins by Penicillium chrysogenum requires supplementation of the growth media with the side-chain precursor adipic acid. In glucose-limited chemostat cultures of P. chrysogenum, up to 88% of the consumed adipic acid was not recovered in cephalosporin-related products, but used as an additional carbon and energy source for growth. This low efficiency of side-chain precursor incorporation provides an economic incentive for studying and engineering the metabolism of adipic acid in P. chrysogenum. Chemostat-based transcriptome analysis in the presence and absence of adipic acid confirmed that adipic acid metabolism in this fungus occurs via β-oxidation. A set of 52 adipate-responsive genes included six putative genes for acyl-CoA oxidases and dehydrogenases, enzymes responsible for the first step of β-oxidation. Subcellular localization of the differentially expressed acyl-CoA oxidases and dehydrogenases revealed that the oxidases were exclusively targeted to peroxisomes, while the dehydrogenases were found either in peroxisomes or in mitochondria. Deletion of the genes encoding the peroxisomal acyl-CoA oxidase Pc20g01800 and the mitochondrial acyl-CoA dehydrogenase Pc20g07920 resulted in a 1.6- and 3.7-fold increase in the production of the semi-synthetic cephalosporin intermediate adipoyl-6-APA, respectively. The deletion strains also showed reduced adipate consumption compared to the reference strain, indicating that engineering of the first step of β-oxidation successfully redirected a larger fraction of adipic acid towards cephalosporin biosynthesis.
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Veiga T,Gombert AK,Landes N,Verhoeven MD,Kiel JA,Krikken AM,Nijland JG,Touw H,Luttik MA,van der Toorn JC,Driessen AJ,Bovenberg RA,van den Berg MA,van der Klei IJ,Pronk JT,Daran JMdoi
10.1016/j.ymben.2012.02.004subject
Has Abstractpub_date
2012-07-01 00:00:00pages
437-48issue
4eissn
1096-7176issn
1096-7184pii
S1096-7176(12)00014-6journal_volume
14pub_type
杂志文章abstract：:A 2D-NMR method based on zero-quantum filtered (ZQF-) TOtal Correlation SpectroscopY (TOCSY) was applied to measure 13C-enrichments in complex mixtures of 13C-labeled metabolites generated in carbon-labeling experiments. Using ZQF-TOCSY, more than 30 13C-enrichments could be potentially measured from the analysis of a...
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pub_type： 杂志文章,评审
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journal_title：Metabolic engineering
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