PT  - JOURNAL ARTICLE
AU  - Carsten Pohl
AU  - Fabiola Polli
AU  - Tabea Schütze
AU  - Annarita Viggiano
AU  - László Mózsik
AU  - Sascha Jung
AU  - Maaike de Vries
AU  - Roel A.L. Bovenberg
AU  - Vera Meyer
AU  - Arnold J.M. Driessen
TI  - A <em>Penicillium rubens</em> platform strain for secondary metabolite production
AID  - 10.1101/2020.04.05.026286
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.05.026286
4099  - http://biorxiv.org/content/early/2020/04/05/2020.04.05.026286.short
4100  - http://biorxiv.org/content/early/2020/04/05/2020.04.05.026286.full
AB  - We present a Penicillium rubens strain with an industrial background in which the four highly expressed biosynthetic gene clusters (BGC) required to produce penicillin, roquefortine, chrysogine and fungisporin were removed. This resulted in a minimal secondary metabolite background. Amino acid pools under steady-state growth conditions showed reduced levels of methionine and increased intracellular aromatic amino acids. Expression profiling of remaining BGC core genes and untargeted mass spectrometry did not identify products from uncharacterized BGCs. This platform strain was repurposed for expression of the recently identified polyketide calbistrin gene cluster and achieved high yields of decumbenone A, B and C. The penicillin BGC could be restored through in vivo assembly with eight DNA segments with short overlaps. Our study paves the way for fast combinatorial assembly and expression of biosynthetic pathways in a fungal strain with low endogenous secondary metabolite burden.