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Metabolites
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Bioactive Metabolites from Fungal Endophytes Associated with Plants
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Bioactive Metabolites from Fungal Endophytes Associated with Plants

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Plant Metabolism".

Deadline for manuscript submissions: closed (22 May 2026) | Viewed by 2377

Special Issue Editors

Prof. Dr. Zhong-Hua Tang

E-Mail Website
Guest Editor
College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China
Interests: medicinal plants secondary metabolism; natural product discovery; multi-omics analysis; medicinal plant stress resistance; plant-microbe interactions
Special Issues, Collections and Topics in MDPI journals
Dr. Chun-Hao Chang

E-Mail Website
Guest Editor
College of Horticulture and Forestry, Tarim University, Alar 843300, China
Interests: microRNA regulation of secondary metabolite biosynthesis; molecular design breeding in ornamental horticulture; light signaling; monoterpene indole alkaloids biosynthesis

Special Issue Information

Dear Colleagues,

This Special Issue focuses on endophytic fungi that are symbiotic with plants as a strategic reservoir of novel bioactive molecules, where unique ecological microenvironments drive the evolution of structurally diverse secondary metabolites (e.g., polyketides, terpenoids, and non-ribosomal peptides). Revolutionary advances in spatial metabolomics and CRISPR-Cas-mediated biosynthetic gene cluster (BGC) editing have enabled unprecedented deciphering of metabolic crosstalk networks within host–microbe symbiotic systems. This Special Issue is devoted to metabolomics in endophytic fungi that are symbiotic with plants, and the topics we aim to cover include (but are not limited to) the following:

  1. Multi-omics-driven elucidation of metabolic networks and BGC discovery in plant-symbiotic endophytes;
  2. Metabolomics-driven identification of pharmacologically active natural products;
  3. The symbiotic interplay between endophytic fungi and their host plants.

Furthermore, we emphasize translational applications, including bioengineered heterologous expression of high-value metabolites and sustainable bioproduction platforms that can be used to replace wild plant extraction.

Prof. Dr. Zhong-Hua Tang
Dr. Chun-Hao Chang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • plants
  • fungal endophytes
  • bioactive metabolites
  • symbiotic interaction
  • biosynthetic gene clusters
  • plant–microbe co-evolution
  • natural product discovery
  • metabolomics
  • synthetic biology
  • antimicrobial activity

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Published Papers (2 papers)

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Research

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22 pages, 18258 KB  
Article
Physiology, Metabolomics, and Transcriptomics Reveal Effects of AMF and Chaetomium globosum Co-Inoculation on Growth and Medicinal Compounds in Astragalus membranaceus
by Yuxin Gong, Shengnan Liu, Xiaoju Zhao, Weisan Zhang, Jiaotong Li, Mengqi Liu, Xueqi Zhang, Hanqi Jia and Zhonghua Tang
Metabolites 2026, 16(5), 313; https://doi.org/10.3390/metabo16050313 - 3 May 2026
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Abstract
Background/Objectives: Microbial inoculants effectively alleviate inhibitory factors during plant cultivation; however, the effects and underlying mechanisms of arbuscular mycorrhizal fungi (AMF) and Chaetomium globosum on the growth, metabolism, and bioactive compound production of A. membranaceus are still poorly understood. Methods: In this [...] Read more.
Background/Objectives: Microbial inoculants effectively alleviate inhibitory factors during plant cultivation; however, the effects and underlying mechanisms of arbuscular mycorrhizal fungi (AMF) and Chaetomium globosum on the growth, metabolism, and bioactive compound production of A. membranaceus are still poorly understood. Methods: In this experiment, different concentrations of C. globosum (104, 106, 108 spores/mL) (Q1, Q2, Q3), AMF, and their combined treatments (AQ1, AQ2, AQ3) were applied to A. membranaceus seedlings via root irrigation, with an equal amount of sterile water as a control (CK). Results: The results showed that: (1) Under single inoculation with C. globosum, root colonization rate increased with higher inoculation concentrations, reaching its peak at Q3. Additionally, AQ3 significantly enhanced AMF colonization in A. membranaceus, and the presence of C. globosum promoted AMF root colonization and expansion. (2) AQ3 significantly enhanced the growth and photosynthesis of A. membranaceus, while also demonstrating excellent efficacy in alleviating lipid peroxidation-induced damage. (3) AQ3 treatment led to increased accumulation of major bioactive compounds in A. membranaceus, including calycosin-7-glucoside, cycloastragenol, and astragalosides I–III. (4) AQ3 treatment significantly upregulated multiple key structural genes involved in phenylalanine metabolism and flavonoid biosynthesis pathways, including PAL, 4CL, FLS, and CYP75B1. Conclusions: This upregulation enhanced the metabolic flux allocation from L-phenylalanine toward downstream flavonoid metabolites, thereby promoting the accumulation of major flavonoid constituents of A. membranaceus, such as galangin and luteolin, in both roots and leaves. Full article
(This article belongs to the Special Issue Bioactive Metabolites from Fungal Endophytes Associated with Plants)
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Review

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29 pages, 1472 KB  
Review
Chemical Signaling and Metabolomic Crosstalk in Endophytic Fungi–Medicinal Plant Symbioses for Natural Product Discovery and Sustainable Bioproduction
by Zhuo Chen and Shilong Jiang
Metabolites 2026, 16(3), 164; https://doi.org/10.3390/metabo16030164 - 28 Feb 2026
Cited by 2 | Viewed by 1405
Abstract
Background: Medicinal plants function as complex holobionts, with their therapeutic potential significantly shaped by the associated microbiome, particularly endophytic fungi. These symbionts engage in a sophisticated “chemical signaling” with their hosts, acting as biotic elicitors that modulate plant secondary metabolism while simultaneously responding [...] Read more.
Background: Medicinal plants function as complex holobionts, with their therapeutic potential significantly shaped by the associated microbiome, particularly endophytic fungi. These symbionts engage in a sophisticated “chemical signaling” with their hosts, acting as biotic elicitors that modulate plant secondary metabolism while simultaneously responding to host cues to activate their own cryptic biosynthetic gene clusters (BGCs). This review aims to critically summarize the multi-layered mechanisms driving this metabolic crosstalk and evaluate strategies to harness this symbiotic intelligence for natural product discovery. Methods: A systematic literature survey spanning the last decade was conducted across major databases. The search specifically targeted studies investigating endophytic fungi in medicinal plants, focusing on experimental designs for BGC activation, applications of spatial metabolomics (matrix-assisted laser desorption/ionization mass spectrometry imaging, MALDI-MSI), and the structural elucidation of novel bioactive natural products through co-culture or in planta models. Results: Our analysis reveals that host-derived chemical cues, such as specific root exudates and oxylipins, act as primary triggers to awaken silent fungal BGCs. We collated numerous recently discovered bioactive metabolites—including novel polyketides, highly rearranged terpenoids, and unique alkaloids—demonstrating their potent antimicrobial and cytotoxic properties. Furthermore, a critical evaluation of spatial metabolomics studies demonstrates that metabolic exchange is highly localized at the plant–fungus interface, providing contextual insights that traditional bulk tissue extraction fails to capture. Conclusions: This review bridges the gap between ecological understanding and synthetic biology applications. We conclude that translating the mechanisms of this “chemical signaling” into biotechnological strategies offers a sustainable pathway for the bioproduction of high-value pharmaceuticals, thereby reducing reliance on the wild harvesting of medicinal plants. Full article
(This article belongs to the Special Issue Bioactive Metabolites from Fungal Endophytes Associated with Plants)
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