Comprehensive transcriptomic and proteomic analyses of antroquinonol biosynthetic genes and enzymes in Antrodia camphorata

Abstract

Antroquinonol (AQ) has several remarkable bioactivities in acute myeloid leukaemia and pancreatic cancer, but difficulties in the mass production of AQ hamper its applications. Currently, molecular biotechnology methods, such as gene overexpression, have been widely used to increase the production of metabolites. However, AQ biosynthetic genes and enzymes are poorly understood. In this study, an integrated study coupling RNA-Seq and isobaric tags for relative and absolute quantitation (iTRAQ) were used to identify AQ synthesis-related genes and enzymes in Antrodia camphorata during coenzyme Q 0-induced fermentation (FM). The upregulated genes related to acetyl-CoA synthesis indicated that acetyl-CoA enters the mevalonate pathway to form the farnesyl tail precursor of AQ. The metE gene for an enzyme with methyl transfer activity provided sufficient methyl groups for AQ structure formation. The CoQ2 and ubiA genes encode p-hydroxybenzoate polyprenyl transferase, linking coenzyme Q 0 and the polyisoprene side chain to form coenzyme Q 3. NADH is transformed into NAD+ and releases two electrons, which may be beneficial for the conversion of coenzyme Q 3 to AQ. Understanding the biosynthetic genes and enzymes of AQ is important for improving its production by genetic means in the future.

Understanding the Essential Metabolic Nodes in the Synthesis of 4-Acetylantroquinol B (4-AAQB) by Antrodia cinnamomea Using Transcriptomic Analysis

“…The expression levels of PPT1/2 were significantly upregulated in the cultivation of A. cinnamomea in the fructose-based medium, which meant that fructose could promote the ligation of OA to FPPB to improve the synthesis of FOAB, as shown in Figure 7. P450 enzymes are the most common oxidase family in the fungal metabolism, which generally catalyzes the oxidation process in metabolite synthesis, and has been found to be closely related to the oxidation synthesis of antroquinonol [27]. In 4-AAQB synthesis, P450 enzymes catalyzed the oxidation of 1-decarboxylation-3-farnesyl pyrophosphate B-orsellinic acid to 6-hydroxyl-5-demethoxylation-coenzyme Q3 B, as shown in Figure 7.…”

Characterization of Cinnamomum kanehirae Extract-Stimulated Triterpenoids Synthesis in Submerged Fermentation of Antrodia camphorata via Untargeted Metabolomics

“…Several studies have been conducted to mitigate this situation and increase the production of bioactive secondary metabolites by adding chemicals or changing culture conditions. − Other research used omics techniques and genetic manipulation to identify and overexpress key genes involved in the synthetic pathway of bioactive compounds in A. camphorata mycelia. , The addition of water-soluble fractions from C. kanehirae could increase the biomass and content of lanostane-type compounds in submerged fermentation of A.…”

“…14−17 Other research used omics techniques and genetic manipulation to identify and overexpress key genes involved in the synthetic pathway of bioactive compounds in A. camphorata mycelia. 18,19 The addition of water-soluble fractions from C. kanehirae could increase the biomass and content of lanostane-type compounds in submerged fermentation of A. camphorata, 20 while the underlying mechanism of the host-stimulated growth and metabolism of A. camphorata remains unknown.…”