A novel role for butyrolactone I as a quorum sensing molecule in the filamentous fungus Aspergillus terreus is proposed based on its ability to affect both lovastatin and its own production. In this work, the exogenous addition of 100 nM butyrolactone I at 96 h post-inoculation to submerged cultures of A. terreus in 5 L bioreactors resulted in 2.5-fold increase in lovastatin production as compared to control cultures at 168 h. An increase in endogenous butyrolactone I levels (2.5-fold) is also detected in cultures supplemented with butyrolactone I, thus suggesting an auto-stimulatory function. Molecular analysis of butyrolactone I-mediated enhancement of lovastatin production revealed induction of lovastatin biosynthetic genes, lovB and lovF, at the transcriptional level. Microarray analysis of A. terreus transcriptome depicted a growth phase-specific response to butyrolactone I addition as the majority of the expressed genes showed differential expression during the specific growth phase (p < 0.01). This study demonstrates for the first time the potential of butyrolactone I as a growth phase-specific inducer of the secondary metabolite lovastatin production and shows the auto-stimulatory effect of this molecule on its own production in the filamentous fungus A. terreus. |