PMID- 18555717 OWN - NLM STAT- MEDLINE DCOM- 20081209 LR - 20200930 IS - 1096-7184 (Electronic) IS - 1096-7176 (Linking) VI - 10 IP - 5 DP - 2008 Sep TI - Production of the polyketide 6-MSA in yeast engineered for increased malonyl-CoA supply. PG - 246-54 LID - 10.1016/j.ymben.2008.04.005 [doi] AB - The heterologous production of fungal polyketides was investigated using 6-methylsalicylic acid synthase (6-MSAS) as a model polyketide synthase and Saccharomyces cerevisiae as a host. In order to improve the production of 6-MSA by enhancing the supply of precursors, the promoter of the gene (ACC1) encoding acetyl-CoA carboxylase, which catalyzes the conversion of acetyl-CoA to malonyl-CoA, was replaced with a strong, constitutive promoter (TEF1p) in a strain harboring two plasmids carrying the genes encoding 6-MSAS from Penicillium patulum and PPTase from Aspergillus nidulans, respectively. The strain was characterized in batch cultivations with a glucose minimal media (20 g/L), and a 60% increase in 6-MSA titer was observed compared to a strain having the native promoter in front of ACC1. The production of 6-MSA was scaled up by the cultivation in minimal media containing 50 g/L of glucose, and hereby a final titer of 554+/-26 mg/L of 6-MSA was obtained. FAU - Wattanachaisaereekul, Songsak AU - Wattanachaisaereekul S AD - Center for Microbial Biotechnology, Technical University of Denmark, Department of Systems Biology, Denmark. FAU - Lantz, Anna Eliasson AU - Lantz AE FAU - Nielsen, Michael Lynge AU - Nielsen ML FAU - Nielsen, Jens AU - Nielsen J LA - eng PT - Journal Article DEP - 20080510 PL - Belgium TA - Metab Eng JT - Metabolic engineering JID - 9815657 RN - 0 (Macrolides) RN - 0 (Multienzyme Complexes) RN - 0 (Peptide Elongation Factor 1) RN - 0 (Saccharomyces cerevisiae Proteins) RN - 0 (Salicylates) RN - 0 (TEF1 protein, S cerevisiae) RN - 524-14-1 (Malonyl Coenzyme A) RN - 72-89-9 (Acetyl Coenzyme A) RN - EC 1.- (Oxidoreductases) RN - EC 2.3.- (Acyltransferases) RN - EC 2.3.1.- (Acetyltransferases) RN - EC 2.3.1.- (aminoglycoside N1-acetyltransferase) RN - EC 6.- (6-methylsalicylic acid synthetase) RN - EC 6.- (Ligases) RN - L5352FE23Y (6-methylsalicylic acid) SB - IM MH - Acetyl Coenzyme A/genetics/metabolism MH - Acetyltransferases/*biosynthesis/genetics MH - Acyltransferases/*biosynthesis/genetics MH - Aspergillus nidulans/enzymology/genetics MH - Ligases/*biosynthesis/genetics MH - Macrolides/*metabolism MH - Malonyl Coenzyme A/genetics/metabolism MH - Multienzyme Complexes/*biosynthesis/genetics MH - Oxidoreductases/*biosynthesis/genetics MH - Penicillium/enzymology/genetics MH - Peptide Elongation Factor 1/genetics/*metabolism MH - Saccharomyces cerevisiae/*enzymology/genetics/growth & development MH - Saccharomyces cerevisiae Proteins/genetics/*metabolism MH - Salicylates/*metabolism EDAT- 2008/06/17 09:00 MHDA- 2008/12/17 09:00 CRDT- 2008/06/17 09:00 PHST- 2007/10/01 00:00 [received] PHST- 2008/02/04 00:00 [revised] PHST- 2008/04/28 00:00 [accepted] PHST- 2008/06/17 09:00 [pubmed] PHST- 2008/12/17 09:00 [medline] PHST- 2008/06/17 09:00 [entrez] AID - S1096-7176(08)00019-0 [pii] AID - 10.1016/j.ymben.2008.04.005 [doi] PST - ppublish SO - Metab Eng. 2008 Sep;10(5):246-54. doi: 10.1016/j.ymben.2008.04.005. Epub 2008 May 10.