Optimization of heterologous production of the polyketide 6-MSA in Saccharomyces cerevisiae

Songsak Wattanachaisaereekul, Anna Eliasson Lantz*, Michael Lynge Nielsen, Ólafur S. Andrésson, Jens Nielsen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Polyketides are a group of natural products that have gained much interest due to their use as antibiotics, cholesterol lowering agents, immunosuppressors, and as other drugs. Many organisms that naturally produce polyketides are difficult to cultivate and only produce these metabolites in small amounts. It is therefore of general interest to transfer polyketide synthase (PKS) genes from their natural sources into heterologous hosts that can overproduce the corresponding polyketides. In this study we demonstrate the heterologous expression of 6-methylsalicylic acid synthase (6-MSAS), naturally produced by Penicillium patulum, in the yeast Saccharomyces cerevisiae. In order to activate the PKS a 4′-phosphopantetheinyl transferase (PPTase) is required. We therefore co-expressed PPTases encoded by either sfp from Bacillus subtilis or by npgA from Aspergillus nidulans. The different strains were grown in batch cultures. Growth and product concentration were measured and kinetic parameters were calculated. It was shown that both PPTases could be efficiently used for activation of PKS's in yeast as good yields of 6-MSA were obtained with both enzymes.

Original languageEnglish
Pages (from-to)893-900
Number of pages8
JournalBiotechnology and Bioengineering
Volume97
Issue number4
DOIs
Publication statusPublished - 1 Jul 2007

Other keywords

  • 4′- phosphopantetheinyl transferase
  • Fermentation kinetics
  • Metabolic engineering
  • Polyketide

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