A methyltransferase LaeA regulates ganoderic acid biosynthesis in Ganoderma lingzhi

Abstract

The methyltransferase LaeA is a global regulator involved in the biosynthesis of secondary metabolites by ascomycete fungi. However, little is known of its regulatory role in basidiomycete fungi. In this study, the laeA gene was identified in the basidiomycete Ganoderma lingzhi and its function in regulating the biosynthesis of anti-tumor ganoderic acids was evaluated. A laeA deletion (ΔlaeA) Ganoderma strain exhibited significantly reduced concentration of ganoderic acids. qRT-PCR analysis further revealed that the transcription levels of genes involved in the biosynthesis of ganoderic acids were drastically lower in the ΔlaeA strain. Moreover, deletion of laeA resulted in decreased accumulation of intermediates and abundances of asexual spores in liquid static culture of G. lingzhi. In contrast, constitutive overexpression of laeA resulted in increased concentration of ganoderic acids. These results demonstrate an essential role of LaeA in the regulation of ganoderic acid biosynthesis in Ganoderma.

AfLaeA, a Global Regulator of Mycelial Growth, Chlamydospore Production, Pathogenicity, Secondary Metabolism, and Energy Metabolism in the Nematode-Trapping Fungus Arthrobotrys flagrans

“…LaeA regulates the expression of multiple secondary metabolic gene clusters and affects the formation of secondary metabolites. Loss of the LaeA gene hindered the expression of multiple secondary metabolic gene clusters, including kojic acid, cyclopiazonic acid, citrinin, citric acid, and the lovastatin gene cluster ( 2 , 30 , 69 – 71 ). In Valsa mali , about half (31/60) of the secondary metabolism gene clusters are regulated by VmLaeA ( 15 ).…”

“…In addition, it has been commonly observed that the overexpression of LaeA has been successfully used to activate some gene clusters, enhance production of several secondary metabolites, and produce new compounds in fungi ( 45 ). Overexpression of LaeA increases the transcription and product formation of genes involved in the kojic acid antitumor compounds terrequinone A, cyclopinionic acid, and tertrimilone ( 2 , 30 , 69 – 72 ). Moreover, overexpression of LaeA results in the production of the novel compound in Aspergillus versicolor 0312 ( 73 ), Chaetomium globosum ( 29 ), and Penicillium dipodomyis YJ-11 ( 74 ), respectively.…”

“…Apart from Aspergillus spp., LaeA is evidently essential for sporulation in other filamentous fungi. LaeA positively regulates the conidial production of Trichoderma spp., including Trichoderma longibrachiatum SMF2Shi, T. atroviride , and T. reesei ( 24 , 25 ), Penicillium spp., including P. oxalicum , P. chrysogenum , and P. expansum ( 26 – 28 ), Chaetomium globosum ( 29 ), A. alternata ( 16 ), and Ganoderma lingzhi ( 30 ) but negatively regulates the conidial production of C. heterostrophus ( 17 ) and M. ruber ( 21 ). LaeA is crucial for development in filamentous fungi.…”

Germplasm resources and secondary metabolism regulation in Reishi mushroom (Ganoderma lucidum)

“…Lanosterol synthase (LS), farnesyl pyrophosphate synthase (FPS), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) and squalene synthase (SQS) are the key enzymes in the ganoderic acid synthesis pathway ( Shi, Ren, Mu, & Zhao, 2010 ). The synthesis of lanosterol from 2,3-epoxysqualene is catalyzed by LS, and the expression of lanosterol synthase gene and the content of ganoderic acid are positively correlated ( Luo, Li, & Xu, 2022 ). LaeA is a global regulatory gene, and the production of ganoderic acid is positively correlated with the transcription level of LaeA gene ( Luo et al, 2022 ).…”

“…The synthesis of lanosterol from 2,3-epoxysqualene is catalyzed by LS, and the expression of lanosterol synthase gene and the content of ganoderic acid are positively correlated ( Luo, Li, & Xu, 2022 ). LaeA is a global regulatory gene, and the production of ganoderic acid is positively correlated with the transcription level of LaeA gene ( Luo et al, 2022 ). HMGR is the rate-limiting enzyme which is responsible for catalyzing the reduction of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonate ( Zhao, Zhong, Liang, Wang, & Jong, 2004 ).…”