TY  - JOUR
A1  - Hitschler, Julia
A1  - Boles, Eckhard
T1  - De novo production of aromatic m-cresol in Saccharomyces cerevisiae mediated by heterologous polyketide synthases combined with a 6-methylsalicylic acid decarboxylase
T2  - Metabolic engineering communications
N2  - 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.
KW  - 6-Methylsalicylic acid synthase
KW  - m-Cresol
KW  - 6-Methylsalicylic acid decarboxylase
KW  - Polyketide synthase
KW  - Codon-optimization
KW  - Saccharomyces cerevisiae
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51059
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-510592
SN  - 2214-0301
N1  - © 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/)
VL  - 9
IS  - e00093
SP  - 1
EP  - 8
PB  - Elsevier
CY  - Amsterdam [u. a.]
ER  -