pks63787, a polyketide synthase gene responsible for the biosynthesis of benzenoids in the medicinal mushroom Antrodia cinnamomea

Antrodia cinnamomea, a unique resupinate basidiomycete endemic to Taiwan, has potent medicinal activities [1]. The reddish basidiocarps and mycelia generally exhibit abundant metabolites with important biological activities [2]. The present study focuses on the functional characterization of the polyketide synthase (PKS) gene, and the change on the secondary metabolites profile. To elucidate the biosynthesis of these pigments, A. cinnamomea PKS genes were characterized and a gene disruption platform was established via protoplast transformation. pks63787 was selected from four putative PKS genes, and disrupted in the monokaryotic wild-type (wt) strain f101. The pks63787 deletion mutant (Δpks63787) was deficient in the synthesis of a series of C₇ benzenoid derivatives, including antroquinonol, a product identified from A. cinnamomea with notable bioactivities [3]. Furthermore, the phylogenic analysis suggests that PKS63787 is a putative orsellinic acid synthase. The pks63787 deletion mutant not only displayed a reduced red phenotype compared to the wt strain but also displayed less 1,1-biphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity. However, the mutant strain Δpks63787 presented same morphology and metabolic profile compared with those of the wt under the optimal concentration of supplemented orsellinic acid in cultural medium. These findings suggest that pks63787 is responsible for the biosynthesis of pigments and metabolites related to the antioxidant activity of A. cinnamomea, and the benzenoid constituents and their related derivatives antroquinonols in A. cinnamomea are derived from orsellinic acid through polyketide pathway instead of shikimate pathway.

Acknowledgments: This work was supported by the Ministry of Science and Technology, Republic of China. We thank Ms. Shou-Ling Huang, Instrumentation Center of the College of Science, National Taiwan University, for NMR data acquisition and Mr. Chia-Hsiang Wang, Biodiversity Research Center, Academia Sinica, for MS data acquisition.

Keywords: Antrodia cinnamomea, polyketide synthase, benzenoid, antroquinonol, orsellinic acid synthase.

References:

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