Elucidation and modeling of the in-vivo kinetics of enzymes and membrane transporters associated with β-lactam and non-ribosomal peptide production in Penicillium chrysogenum

Abstract

Even 80 years after the discovery of penicillin, it still holds 16% of total antibiotics market. This makes it crucial, from an economical point of view, to improve our understanding of the production organism Penicillium chrysogenum to maximize the penicillin production, as its theoretical yields are far from reached. With the advancement in analytical techniques and detailed knowledge of the metabolic pathways, enough information and tools are available to try to identify possible bottlenecks that limit the penicillin yield, and thus with known genome sequence there are possibilities to modify the strain by using metabolic engineering strategies. One of the aims of this study was to unravel the in vivo enzyme kinetic properties and identify possible bottlenecks in the penicillin biosynthesis pathway in Penicillium chrysogenum. To understand the mechanism of the enzymes/transporters under in vivo conditions and to estimate parameters, several different studies were carried out that included steady state and stimulus response experiments. The other aim of the study was to use Penicillium chrysogenum as a cell factory to produce non-ribosomal peptides. The strain used was an industrial high producing strain.