Identification of a polyketide synthase involved in sorbicillin biosynthesis by Penicillium chrysogenum

Secondary metabolism in Penicillium chrysogenum was intensively subjected to classical strain improvement (CSI) resulting industrial strains producing high levels of β-lactams. During this process, the production of yellow pigments including sorbicillinoids was eliminated as part of a strategy to enable the rapid purification of β-lactams. Here we report the identification of the polyketide synthase (PKS) gene essential for sorbicillinoids biosynthesis in P. chrysogenum We demonstrate that the production of polyketide precursors like sorbicillinol and dihydrosorbicillinol as well as their derivatives bisorbicillinoids require the function of a highly reducing PKS encoded by the gene Pc21g05080 (pks13). This gene belongs to the cluster that was mutated and transcriptionally silenced during the strain improvement program. Using an improved β-lactam producing strain, repair of the mutation in pks13 led to the restoration of sorbicillinoids production. This now enable genetic studies on the mechanism of sorbicillinoid biosynthesis in P. chrysogenum and opens new perspectives for pathway engineering.

IMPORTANCE: Sorbicillinoids are secondary metabolites with anti-viral, anti-inflammatory and anti-microbial activity produced by filamentous fungi. This study identified the gene cluster responsible for sorbicillinoids formation in Penicillium chrysogenum now allow engineering of this diverse group of compounds.