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Engineering of Penicillium chrysogenum for fermentative production of a novel carbamoylated cephem antibiotic precursor

Paper ID Volume ID Publish Year Pages File Format Full-Text
31739 44834 2009 13 PDF Available
Title
Engineering of Penicillium chrysogenum for fermentative production of a novel carbamoylated cephem antibiotic precursor
Abstract

Penicillium chrysogenum was successfully engineered to produce a novel carbamoylated cephalosporin that can be used as a synthon for semi-synthetic cephalosporins. To this end, genes for Acremonium chrysogenum expandase/hydroxylase and Streptomyces clavuligerus carbamoyltransferase were expressed in a penicillinG high-producing strain of P. chrysogenum. Growth of the engineered strain in the presence of adipic acid resulted in production of adipoyl-7-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (ad7-ACCCA) and of several adipoylated pathway intermediates. A combinatorial chemostat-based transcriptome study, in which the ad7-ACCCA-producing strain and a strain lacking key genes in β-lactam synthesis were grown in the presence and absence of adipic acid, enabled the dissection of transcriptional responses to adipic acid per se and to ad7-ACCCA production. Transcriptome analysis revealed that adipate catabolism in P. chrysogenum occurs via β-oxidation and enabled the identification of putative genes for enzymes involved in mitochondrial and peroxisomal β-oxidation pathways. Several of the genes that showed a specifically altered transcript level in ad7-ACCCA-producing cultures were previously implicated in oxidative stress responses.

Keywords
Penicillium chrysogenum; Metabolic engineering; Adipoyl-7-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid; Carbamoylated cephem antibioticsACV, δ-(l-α-aminoadipyl)-l-cysteine-d-valine; ad7-ACCCA, adipoyl-7-amino-3-carbamoyloxymethyl-3-cephem-4-carbo
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Engineering of Penicillium chrysogenum for fermentative production of a novel carbamoylated cephem antibiotic precursor
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 11, Issue 2, March 2009, Pages 125–137
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us