TY  - JOUR
AU  - Lee, Jungho
AU  - Hilgers, Fabienne
AU  - Loeschke, Anita
AU  - Jaeger, Karl-Erich
AU  - Feldbrügge, Michael
TI  - Ustilago maydis Serves as a Novel Production Host for the Synthesis of Plant and Fungal Sesquiterpenoids
JO  - Frontiers in microbiology
VL  - 11
SN  - 1664-302X
CY  - Lausanne
PB  - Frontiers Media
M1  - FZJ-2020-05225
SP  - 1655
PY  - 2020
AB  - Sesquiterpenoids are important secondary metabolites with various pharma- and nutraceutical properties. In particular, higher basidiomycetes possess a versatile biosynthetic repertoire for these bioactive compounds. To date, only a few microbial production systems for fungal sesquiterpenoids have been established. Here, we introduce Ustilago maydis as a novel production host. This model fungus is a close relative of higher basidiomycetes. It offers the advantage of metabolic compatibility and potential tolerance for substances toxic to other microorganisms. We successfully implemented a heterologous pathway to produce the carotenoid lycopene that served as a straightforward read-out for precursor pathway engineering. Overexpressing genes encoding enzymes of the mevalonate pathway resulted in increased lycopene levels. Verifying the subcellular localization of the relevant enzymes revealed that initial metabolic reactions might take place in peroxisomes: despite the absence of a canonical peroxisomal targeting sequence, acetyl-CoA C-acetyltransferase Aat1 localized to peroxisomes. By expressing the plant (+)-valencene synthase CnVS and the basidiomycete sesquiterpenoid synthase Cop6, we succeeded in producing (+)-valencene and α-cuprenene, respectively. Importantly, the fungal compound yielded about tenfold higher titers in comparison to the plant substance. This proof of principle demonstrates that U. maydis can serve as promising novel chassis for the production of terpenoids.
LB  - PUB:(DE-HGF)16
C6  - 32849341
UR  - <Go to ISI:>//WOS:000560547000001
DO  - DOI:10.3389/fmicb.2020.01655
UR  - https://juser.fz-juelich.de/record/888811
ER  -