Inactivation of the global regulator LaeA in Monascus ruber results in a species-dependent response in sporulation and secondary metabolism

• LaeA is a global regulator in Monascus ruber, a kind of traditional fermented fungi.
• We firstly discovered the disruption of laeA could lead to the typical cleistothecia disappearing.
• LaeA negatively controlled the vegetative development and the asexual reproduction in M. ruber.
• LaeA positively regulated the sexual reproduction and the secondary metabolism in M. ruber.
• The function of LaeA may be species-dependent, even though its amino acid sequences are well conserved in numerous fungi.

The nuclear regulator LaeA has been proven to globally govern fungal development and secondary metabolism, but its function may be species-dependent, even though its amino acid sequences are well conserved in numerous fungi. Herein we identified the LaeA in Monascus ruber M7 (MrLaeA), and verified its role to mediate growth, sporulation and secondary metabolism. Results showed that the radial growth rate of the selected MrlaeA knock-out mutant (MrΔlaeA-22) was significantly faster than that of the parental strain M. ruber M7, and growth was accompanied by the formation of an abnormal colony phenotype with more abundant aerial hyphae. Interestingly, conidia production of the MrΔlaeA-22 strain was about thrice that of M. ruber M7, but ascospores were not observed in the MrΔlaeA-22 strain. Additionally, compared to M. ruber M7, MrΔlaeA-22 exhibited drastically reduced production of multiple secondary metabolites, especially those of the six well-known Monascus pigments and citrinin. Simultaneously, the selected MrlaeA complementation strain (MrΔlaeA::laeA-45) nearly recovered the capacity for sporulation and secondary metabolism observed in the parental strain. These results demonstrate that MrLaeA regulates not only secondary metabolism, but also asexual and sexual differentiation in M. ruber, but some of its regulation appears to differ from other fungi.

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