The inducers 1,3-diaminopropane and spermidine produce a drastic increase in the expression of the penicillin biosynthetic genes for prolonged time, mediated by the LaeA regulator

• Published in: Fungal genetics and biology 2012-12, Vol.49 (12), p.1004-1013
• Main Authors: Martín, Jorge, García-Estrada, Carlos, Kosalková, Katarina, Ullán, Ricardo V., Albillos, Silvia M., Martín, Juan-Francisco
• Format: Article
• Language: English
• Subjects: Acremonium chrysogenum; benzylpenicillin; biosynthesis; Biosynthetic Pathways - drug effects; Biosynthetic Pathways - genetics; Culture Media - chemistry; Diamines - metabolism; fermenters; Gene Expression - drug effects; Gene Expression Profiling; Gene Knockdown Techniques; genes; heterochromatin; LaeA; metabolites; mutants; mutation; Penicillin biosynthesis; Penicillin G - metabolism; Penicillium chrysogenum; Penicillium chrysogenum - drug effects; Penicillium chrysogenum - metabolism; Polyamines; putrescine; Putrescine - metabolism; Secondary metabolism; spermidine; Spermidine - metabolism; Trans-Activators - metabolism; Transcriptional regulation
• ISSN: 1087-1845; 1096-0937
• DOI: 10.1016/j.fgb.2012.10.001

► 1,3-DAP and spermidine increase the expression of the penicillin biosynthetic genes. ► These polyamines do not affect the expression of the global pH-stress regulator pacC. ► 1,3-DAP and spermidine stimulate the expression of the secondary metabolism global regulator LaeA. We described previously that an autoinducer molecule, identified as 1,3-diaminopropane (1,3-DAP), is secreted by Penicillium chrysogenum and Acremonium chrysogenum. Using pH-controlled fermentor cultures we have observed in this work that 1,3-DAP and spermidine clearly stimulate the biosynthesis of benzylpenicillin in P. chrysogenum, both in defined and in complex penicillin production media. Both 1,3-DAP and spermidine, but not putrescine (1,4-diaminobutane), produce a drastic increase in the transcript levels of the penicillin biosynthetic genes pcbAB, pcbC and penDE. These polyamines do not affect the expression of the global pH-stress regulator pacC gene, thus excluding that the effect of 1,3-DAP and spermidine is due to a modification of the pH control mechanism. Expression of the three penicillin biosynthetic genes is drastically reduced in a laeA-knock-down mutant of P. chrysogenum, which produces very low levels of benzylpenicillin. Interestingly, 1,3-DAP and spermidine revert the effect of the laeA knock-down mutation, completely restoring the levels of penicillin production. Furthermore, 1,3-DAP and spermidine enhanced the expression of laeA in the parental strain and restored the levels of laeA transcripts in the laeA knock-down mutant. Taken together these results indicate that the stimulatory effect of the inducer molecules 1,3-DAP and spermidine is exerted, at least in part, through the stimulation of the expression of laeA, a global regulator that acts epigenetically on the expression of secondary metabolite genes by heterochromatin reorganization.