title: 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.
abstract: 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.
authors.affiliation: INBIOTEC, Instituto de Biotecnología de León, Avda. Real n°. 1, Parque Científico de León, 24006 León, Spain. jf.martin@unileon.es
authors.forename: Jorge
authors.initials: J
authors.lastname: Martín
authors.forename: Carlos
authors.initials: C
authors.lastname: García-Estrada
authors.forename: Katarina
authors.initials: K
authors.lastname: Kosalková
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Ullán
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Albillos
authors.forename: Juan-Francisco
authors.initials: JF
authors.lastname: Martín
mesh_terms: D053898:Biosynthetic Pathways / Q000187:drug effects* / Q000235:genetics; D003470:Culture Media / Q000737:chemistry; D003959:Diamines / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D010400:Penicillin G / Q000378:metabolism*; D010408:Penicillium chrysogenum / Q000187:drug effects / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D003470:Culture Media; D003959:Diamines; D015534:Trans-Activators; C009475:trimethylenediamine; D010400:Penicillin G; D013095:Spermidine; D011700:Putrescine