Strain Improvement by Overexpression of the laeA Gene in Monascus pilosus for the Production of Monascus-Fermented Rice

Abstract

Monascus species have been used to produce fermented rice called Monascus-fermented rice (MFR). To improve a Monascus strain via activation of secondary metabolite (SM) gene clusters for use in the production of MFR, we overexpressed an ortholog of the laeA gene, which encodes a global positive regulator of secondary metabolism under the control of the strong heterologous Aspergillus nidulans alcA promoter in Monascus pilosus. The OE::laeA transformant produced more SMs, including those not detected under uninduced conditions. MFR produced using the M. pilosus OE::laeA strain contained 4 times more monacolin K, a cholesterol-lowering agent, than MFR produced using the wild-type strain. In addition, pigment production was remarkably increased, and the antioxidant activity was increased as well. The results from this study suggest that Monascus species, which are important industrial fermentative fungi in Asia, can be improved for the production of functional foods by overexpressing the laeA gene.

Edible Filamentous Fungi from the Species Monascus: Early Traditional Fermentations, Modern Molecular Biology, and Future Genomics

“…An MrflbA ‐deleted mutant resulted in lower production of pigment and citrinin (Yang and others ). The downregulation of MpLaeA by transgenic antisense d‐MpLaeA cDNA resulted in less production of monacolin K in M. pilosus (Zhang and Miyake ), whereas overexpressing the laeA gene in M. pilosus remarkably increased the production of monacolin K and pigments (Lee and others ).…”

Effects of Chinese medicines on monacolin K production and related genes transcription of Monascus ruber in red mold rice fermentation

“…The gene mokH is encoding transcription factor acting as the linker region of GAL4 and PPR1 and is regarded as the activator for MK production (Chen, Yuan, et al, 2013). Moreover, the methyltransferase gene ( laeA ) is regarded as a global regulator for secondary metabolites cluster of filamentous fungi (Lee, Lee, & Lee, 2013), and deletion of laeA blocks the expression of several secondary metabolite gene cluster (Bok & Keller, 2004). In M. pilosus , a similar methyltransferase gene ( mplaeA ) is found to have similar conserved region, and down‐regulation of mplaeA resulted in the decrease of MK production (Zhang & Miyake, 2009).…”

Epigenetics as an emerging tool for improvement of fungal strains used in biotechnology

“…MFR is also used as a folk medicine to improve blood circulation and spleen and stomach health, and most of the health-promoting compounds have been identified to be fungal secondary metabolites. Lee et al (2013) therefore overexpressed the Monascus pilosus laeA ortholog under the control of the strong Aspergillus nidulans alcA promoter. The resulting OE:laeA transformant produced four times more secondary metabolites such monacolin K, a cholesterol-lowering agent, and also components not detected under the same conditions in the parent strain.…”