Strategies for the Enhancement of Secondary Metabolite Production via Biosynthesis Gene Cluster Regulation in Aspergillus oryzae

Abstract

The filamentous fungus Aspergillus oryzae (A. oryzae) has been extensively used for the biosynthesis of numerous secondary metabolites with significant applications in agriculture and food and medical industries, among others. However, the identification and functional prediction of metabolites through genome mining in A. oryzae are hindered by the complex regulatory mechanisms of secondary metabolite biosynthesis and the inactivity of most of the biosynthetic gene clusters involved. The global regulatory factors, pathway-specific regulatory factors, epigenetics, and environmental signals significantly impact the production of secondary metabolites, indicating that appropriate gene-level modulations are expected to promote the biosynthesis of secondary metabolites in A. oryzae. This review mainly focuses on illuminating the molecular regulatory mechanisms for the activation of potentially unexpressed pathways, possibly revealing the effects of transcriptional, epigenetic, and environmental signal regulation. By gaining a comprehensive understanding of the regulatory mechanisms of secondary metabolite biosynthesis, strategies can be developed to enhance the production and utilization of these metabolites, and potential functions can be fully exploited.

Keywords: Aspergillus oryzae; regulatory gene; secondary metabolism; secondary metabolites.

Figure 1

Regulatory network of secondary metabolism in filamentous fungi.

Figure 2

A schematic representation of the global regulation of the LaeA and Velvet family proteins. Importin alpha KapA facilitates the nuclear entry of the VelB-VeA dimer. VelB can assemble into two distinct complexes within the nucleus. The VosA-VelB dimer suppresses asexual spore formation while regulating spore maturation and trehalose synthesis. The VelB-VeA dimer interacts with the LaeA protein to form a trimer, which modulates sexual development and secondary metabolism.

Figure 3

Epigenetic regulatory patterns of secondary metabolites in fungi.

Figure 4

Environmental regulation of biosynthetic gene clusters for secondary metabolites in fungi. Environmental signals regulate the expressions of genes in biosynthetic gene clusters, thereby controlling the activities of key enzymes or gene expression levels in secondary metabolic pathways and ultimately affecting the synthesis of secondary metabolites. The intracellular molecule cAMP mediates the internal regulation of biosynthetic gene clusters by modulating camp-dependent protein kinase (PKA).

Figure 5

Activation of the recessive gene cluster and strategies for mining novel compounds in A. oryzae.