De novo production of aromatic m-cresol in Saccharomyces cerevisiae mediated by heterologous polyketide synthases combined with a 6-methylsalicylic acid decarboxylase

  • As a flavor and platform chemical, m-cresol (3-methylphenol) is a valuable industrial compound that currently is mainly synthesized by chemical methods from fossil resources. In this study, we present the first biotechnological de novo production of m-cresol from sugar in complex yeast extract-peptone medium with the yeast Saccharomyces cerevisiae. A heterologous pathway based on the decarboxylation of the polyketide 6-methylsalicylic acid (6-MSA) was introduced into a CEN.PK yeast strain. For synthesis of 6-MSA, expression of different variants of 6-MSA synthases (MSASs) were compared. Overexpression of codon-optimized MSAS from Penicillium patulum together with activating phosphopantetheinyl transferase npgA from Aspergillus nidulans resulted in up to 367 mg/L 6-MSA production. Additional genomic integration of the genes had a strongly promoting effect and 6-MSA titers reached more than 2 g/L. Simultaneous expression of 6-MSA decarboxylase patG from A. clavatus led to the complete conversion of 6-MSA and production of up to 589 mg/L m-cresol. As addition of 450–750 mg/L m-cresol to yeast cultures nearly completely inhibited growth our data suggest that the toxicity of m-cresol might be the limiting factor for higher production titers.
Metadaten
Author:Julia HitschlerGND, Eckhard BolesORCiD
URN:urn:nbn:de:hebis:30:3-510592
DOI:https://doi.org/10.1016/j.mec.2019.e00093
ISSN:2214-0301
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31193192
Parent Title (English):Metabolic engineering communications
Publisher:Elsevier
Place of publication:Amsterdam [u. a.]
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/05/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/09/16
Tag:6-Methylsalicylic acid decarboxylase; 6-Methylsalicylic acid synthase; Codon-optimization; Polyketide synthase; Saccharomyces cerevisiae; m-Cresol
Volume:9
Issue:e00093
Page Number:8
First Page:1
Last Page:8
Note:
© 2019 The Authors. Published by Elsevier B.V. on behalf of International Metabolic Engineering Society. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
HeBIS-PPN:454014880
Institutes:Biowissenschaften / Biowissenschaften
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Biochemie, Chemie und Pharmazie
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0