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Heterologous production of non-ribosomal peptide LLD-ACV in Saccharomyces cerevisiae

Paper ID Volume ID Publish Year Pages File Format Full-Text
31799 44839 2009 7 PDF Available
Title
Heterologous production of non-ribosomal peptide LLD-ACV in Saccharomyces cerevisiae
Abstract

Non-ribosomal peptides (NRPs) are a diverse family of secondary metabolites with a broad range of biological activities. We started to develop an eukaryotic microbial platform based on the yeast Saccharomyces cerevisiae for heterologous production of NRPs using δ-(l-α-aminoadipyl)–l-cysteinyl–d-valine (ACV) as a model NRP. The Penicillium chrysogenum gene pcbAB encoding ACV synthetase was expressed in S. cerevisiae from a high-copy plasmid together with phosphopantetheinyl transferase (PPTase) encoding genes from Aspergillus nidulans, P. chrysogenum and Bacillus subtilis, and in all the three cases production of ACV was observed. To improve ACV synthesis, several factors were investigated. Codon optimization of the 5′ end of pcbAB did not significantly increase ACV production. However, a 30-fold enhancement was achieved by lowering the cultivation temperature from 30 to 20 °C. When ACVS and PPTase encoding genes were integrated into the yeast genome, a 6-fold decrease in ACV production was observed indicating that gene copy number was one of the rate-limiting factors for ACV production in yeast.

Keywords
Secondary metabolites; Non-ribosomal peptide synthetase; Phosphopantetheinyl transferase; S. cerevisiae
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Heterologous production of non-ribosomal peptide LLD-ACV in Saccharomyces cerevisiae
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 11, Issue 6, November 2009, Pages 391–397
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