Production of Aromatic -cresol in Mediated by Heterologous Polyketide Synthases Combined with a 6-methylsalicylic Acid Decarboxylase

Overview

Journal Metab Eng Commun

Specialty Biochemistry

Date 2019 Jun 14

PMID 31193192

Citations 11

Authors

Julia Hitschler

Eckhard Boles

Affiliations

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Abstract

As a flavor and platform chemical, -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 production of -cresol from sugar in complex yeast extract-peptone medium with the yeast . 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 (s) were compared. Overexpression of codon-optimized from together with activating phosphopantetheinyl transferase from 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 from 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 -cresol might be the limiting factor for higher production titers.

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