A mechanistic study on the biosynthetic regulation of bioactive metabolite Antroquinonol from edible and medicinal mushroom Antrodia camphorata

Hu, Yongdan; Zhang, Bobo; Xu, Guowang; Liao, Xiangru; Cheung, Peter C.K.

doi:10.1016/j.jff.2016.05.014

Cited by 16 publications

(12 citation statements)

References 37 publications

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Section: Discussionmentioning

confidence: 99%

“…ACACA , E2.3.3.10 , OXCT , IVD , and PAAH genes, which are associated with acetyl-CoA, were also upregulated. The formation of AQ may be closely related to the ubiquinone biosynthesis pathway (Hu et al 2016 ). The initial biosynthetic pathway of ubiquinone involves the conversion of three acetyl-coA units into farnesyl diphosphate (FPP) (Ericsson et al 1992 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, upregulated metE genes could encode an enzyme (ec:2.1.1.14) with methyltransferase activity. According to the reported results, it is important to have a sufficient supply of methyl groups for AQ structure formation (Wijayasinghe et al 2014 ; Hu et al 2016 ). These results suggest that S -adenosylmethionine synthetase may play a vital role in the biosynthesis of AQ.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…77,78 Thus, CoQ 0 , as a common polyketone compound, was selected as a precursor of ubiquinone derivatives, and the in-depth investigation of the mechanisms revealed that the addition of CoQ 0 could regulate some key proteins involved in the antroquinonol biosynthetic pathway. 74,75,79 Afterward, phylogenetic analysis on the amino acid sequences of the PKS63787 KS domains and 32 NR-PKSs of representing fungal species revealed that pks63787 was clustered with orsellinic acid synthases, which tightly linked with the important precursor of ubiquinone derivatives in A. cinnamomea. 53 Further deletion of pks63787 resulted in the failure of synthesis of antroquinonol and 4-acetylantroquinonol B.…”

Section: Biosynthesis and Metabolicmentioning

confidence: 99%

Current Advances on the Structure, Bioactivity, Synthesis, and Metabolic Regulation of Novel Ubiquinone Derivatives in the Edible and Medicinal Mushroom Antrodia cinnamomea

Zhang

Huang

et al. 2017

J. Agric. Food Chem.

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In recent years, Antrodia cinnamomea has attracted great attention around the world as an extremely precious edible and medicinal mushroom. Ubiquinone derivatives, which are characteristic metabolites of A. cinnamomea, have shown great bioactivities. Some of them have been regarded as promising therapeutic agents and approved into clinical trial by the U.S. Food and Drug Administration. Although some excellent reviews have been published covering different aspects of A. cinnamomea, this review brings, for the first time, complete information about the structure, bioactivity, chemical synthesis, biosynthesis, and metabolic regulation of ubiquinone derivatives in A. cinnamomea. It not only advances our knowledge on the bioactive metabolites, especially the ubiquinone derivatives, in A. cinnamomea but also provides valuable information for the investigation on other edible and medicinal mushrooms.

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“…We analyzed gene expression in A. camphorata at the transcriptional level and showed that genes related to the synthesis pathways of UQ and other terpenoid-quinones were upregulated by adding UQ0 to the in situ extractive fermentation system (Liu et al, 2020 ). UQ0 upregulates the expression of S-adenosylmethionine synthetase and provides a methyl group for the biosynthesis of AQ (Hu et al, 2016 ). Moreover, UQ0 induces the biosynthesis of 4-acetyl-AQ (Chiang et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Genetic evidence for the requirements of antroquinonol biosynthesis byAntrodia camphorataduring liquid-state fermentation

Xia

Zhou

Liang

et al. 2021

Journal of Industrial Microbiology and Biotechnology

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The solid-state fermentation of Antrodia camphorata could produce a variety of ubiquinone compounds, such as antroquinonol (AQ), AQB, 4-acetyl-AQB and so on. However, ubiquinone compounds are hardly synthesized during liquid-state fermentation (LSF) and the mechanism of synthesis remain unclear. To investigates the influence of different precursors on the synthesis of AQ, three exogenous precursors (ubiquinone 0, UQ0; farnesol and farnesyl diphosphate, FPP) were used in LSF. The results showed that UQ0 successfully induced AQ production; however, farnesol and FPP did not play a role in producing AQ. The results of fermentation experiments show that the precursor that restricts the synthesis of AQ is the quinone ring, not the isoprene side chain. An efficient Agrobacterium-mediated transformation system of A. camphorata was established. Exogenous genes were effectively integrated into the genome of A. camphorata using this system. Then, we overexpressed a series of genes for quinone ring modification (coq2-6) and isoprene synthesis (HMGR, fps) by using the ATMT transformation system, which endogenously increased the content of intracellular precursor for AQ biosynthesis in A. camphorata. The results showed that overexpression of genes for isoprene side chain synthesis could not increase the yield of AQ, but overexpression of coq2 and coq5 could significantly increase AQ production. This is consistent with the results of the fermentation experiment with the addition of precursors. It indicated that the A. camphorata lack the ability to modify the quinone ring of AQ during LSF. Of the modification steps, prenylation of UQ0 is the key step of AQ biosynthesis during LSF. The result will help us to understand the genetic evidence for the requirements of antroquinonol biosynthesis in A. camphorata.

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A mechanistic study on the biosynthetic regulation of bioactive metabolite Antroquinonol from edible and medicinal mushroom Antrodia camphorata

Cited by 16 publications

References 37 publications

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

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

Current Advances on the Structure, Bioactivity, Synthesis, and Metabolic Regulation of Novel Ubiquinone Derivatives in the Edible and Medicinal Mushroom Antrodia cinnamomea

Genetic evidence for the requirements of antroquinonol biosynthesis byAntrodia camphorataduring liquid-state fermentation

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