Enhanced Production and Profiling of Ganoderic Acids in Ganoderma lucidum Mycelia via Two-Stage Cultivation and GNPS-Guided Metabolomics

Tsao, Chieh-Hsi; Tsai, Hsin-Ya; Cheng, Kai-Wen; Chen, Guan-Yuan; Chen, Hao-Ting; Hsu, Cheng-Chih; Su, Nan-Wei

doi:10.3390/jof12070500

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Enhanced Production and Profiling of Ganoderic Acids in Ganoderma lucidum Mycelia via Two-Stage Cultivation and GNPS-Guided Metabolomics

by

Chieh-Hsi Tsao

^1,†

,

Hsin-Ya Tsai

^1,†

,

Kai-Wen Cheng

²

,

Guan-Yuan Chen

³,

Hao-Ting Chen

¹,

Cheng-Chih Hsu

^2,4

and

Nan-Wei Su

^1,5,*

¹

Department of Agricultural Chemistry, National Taiwan University, Taipei 106319, Taiwan

²

Leeuwenhoek Laboratories Co., Ltd., Taipei 106070, Taiwan

³

Department and Graduate Institute of Forensic Medicine, College of Medicine, National Taiwan University, Taipei 100225, Taiwan

⁴

Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan

⁵

Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

J. Fungi 2026, 12(7), 500; https://doi.org/10.3390/jof12070500 (registering DOI)

Submission received: 6 June 2026 / Revised: 2 July 2026 / Accepted: 7 July 2026 / Published: 8 July 2026

(This article belongs to the Section Fungal Cell Biology, Metabolism and Physiology)

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Abstract

Ganoderic acids (GAs) are bioactive lanostane-type triterpenoids produced by Ganoderma lucidum that accumulate predominantly in fruiting bodies, whose long cultivation period limits their practical production. Using Global Natural Products Social Molecular Networking (GNPS), we identified G. lucidum TM701, which accumulated 99 GA derivatives in mycelia and exhibited higher triterpenoid levels and greater chemical diversity than the commercial strain BCRC 36203. Four abundant GAs (GA-Mb/Mc, GA-S/Mf, GA-T, and GA-R) were selected as marker compounds for monitoring GA production. A modified two-stage cultivation strategy, combining submerged inoculum preparation with nutrient optimization during static cultivation, increased GA production to 1396 mg L⁻¹ GAs in potato dextrose broth supplemented with 2% glucose. Heat treatment revealed interconversion among GA-Mb/Mc, GA-Mh, and GA-P/Q, indicating a dehydration-driven stabilization of conjugated diene structures. G. lucidum TM701 mycelia not only provide a platform for triterpenoid production, but also serve as a promising model for elucidating GA biosynthesis and investigating their thermal transformation.

Keywords: ganoderic acids; Ganoderma lucidum; GNPS; molecular network; mycelia; triterpenoids

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MDPI and ACS Style

Tsao, C.-H.; Tsai, H.-Y.; Cheng, K.-W.; Chen, G.-Y.; Chen, H.-T.; Hsu, C.-C.; Su, N.-W. Enhanced Production and Profiling of Ganoderic Acids in Ganoderma lucidum Mycelia via Two-Stage Cultivation and GNPS-Guided Metabolomics. J. Fungi 2026, 12, 500. https://doi.org/10.3390/jof12070500

AMA Style

Tsao C-H, Tsai H-Y, Cheng K-W, Chen G-Y, Chen H-T, Hsu C-C, Su N-W. Enhanced Production and Profiling of Ganoderic Acids in Ganoderma lucidum Mycelia via Two-Stage Cultivation and GNPS-Guided Metabolomics. Journal of Fungi. 2026; 12(7):500. https://doi.org/10.3390/jof12070500

Chicago/Turabian Style

Tsao, Chieh-Hsi, Hsin-Ya Tsai, Kai-Wen Cheng, Guan-Yuan Chen, Hao-Ting Chen, Cheng-Chih Hsu, and Nan-Wei Su. 2026. "Enhanced Production and Profiling of Ganoderic Acids in Ganoderma lucidum Mycelia via Two-Stage Cultivation and GNPS-Guided Metabolomics" Journal of Fungi 12, no. 7: 500. https://doi.org/10.3390/jof12070500

APA Style

Tsao, C.-H., Tsai, H.-Y., Cheng, K.-W., Chen, G.-Y., Chen, H.-T., Hsu, C.-C., & Su, N.-W. (2026). Enhanced Production and Profiling of Ganoderic Acids in Ganoderma lucidum Mycelia via Two-Stage Cultivation and GNPS-Guided Metabolomics. Journal of Fungi, 12(7), 500. https://doi.org/10.3390/jof12070500

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Enhanced Production and Profiling of Ganoderic Acids in Ganoderma lucidum Mycelia via Two-Stage Cultivation and GNPS-Guided Metabolomics

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