The inducers 1,3-diaminopropane and spermidine cause the reprogramming of metabolism in Penicillium chrysogenum, leading to multiple vesicles and penicillin overproduction

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In this article we studied the differential protein abundance of Penicillium chrysogenum in response to either 1,3-diaminopropane (1,3-DAP) or spermidine, which behave as inducers of the penicillin production process. Proteins were resolved in 2-DE gels and identified by tandem MS spectrometry. Both inducers produced largely identical changes in the proteome, suggesting that they may be interconverted and act by the same mechanism. The addition of either 1,3-DAP or spermidine led to the overrepresentation of the last enzyme of the penicillin pathway, isopenicillin N acyltransferase (IAT). A modified form of the IAT protein was newly detected in the polyamine-supplemented cultures. Both inducers produced a rearrangement of the proteome resulting in an overrepresentation of enzymes involved in the biosynthesis of valine and other precursors (e.g. coenzyme A) of penicillin. Interestingly, two enzymes of the homogentisate pathway involved in the degradation of phenylacetic acid (a well-known precursor of benzylpenicillin) were reduced following the addition of either of these two inducers, allowing an increase of the phenylacetic acid availability. Both inducers produced also an increase in the intracellular content of vesicles that derived to vacuoles in late stages and promoted sporulation of P. chrysogenum in solid medium. The analysis of global protein changes produced in response to polyamines 1,3-DAP and spermidine provides a valuable information for the understanding of the molecular mechanisms underlying the production of penicillin. This represents useful information to improve the production of this antibiotic and many other bioactive secondary metabolites not only in P. chrysogenum, but in other filamentous fungi as well.