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.
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): | Creative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0 |