Tryptophan-centered metabolic alterations coincides with lipid-mediated fungal response to cold stress

• Published in: Heliyon Vol. 9; no. 2; p. e13066
• Main Authors: Chen, Yonghong, Yang, Xiaoyu, Zhang, Longlong, Wu, Qunfu, Li, Shuhong, Gou, Jianghui, He, Jiangbo, Zhang, Keqin, Li, Shenghong, Niu, Xuemei
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2023; Elsevier
• Subjects: Cold stress; Lipids; Prenylated indole alkaloids; Thermomyces dupontii; Tryptophan; Tryptophan metabolism; Thermomyces dupontii; Cold stress; Prenylated indole alkaloids; Tryptophan metabolism; Tryptophan; Lipids; TEM; PIAs; PIAs, prenyl indole alkaloids; TEM, transmission electron microscope
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2023.e13066

Tryptophan and its derived metabolites have been assumed to play important roles in the development and survival of organisms. However, the links of tryptophan and its derived metabolites to temperature change remained largely cryptic. Here we presented that a class of prenyl indole alkaloids biosynthesized from tryptophan dramatically accumulated in thermophilic fungus Thermomyces dupontii under cold stress, in which lipid droplets were also highly accumulated and whose conidiophores were highly build-up. Concurrently, disruption of the key NRPS gene involved in the biosynthesis of prenyl indole alkaloids, resulted in decreased lipid and shrunken mitochondria but enlarged vacuoles. Moreover, the Fe3+ and superoxide levels in ΔNRPS were significantly increased but the reactive oxygen species lipid peroxidation and autophagy levels decreased. Metabolomics study revealed that most enriched metabolites in ΔNRPS were mainly composed of tryptophan degraded metabolites including well known ROS scavenger kynurenamines, and lipid-inhibitors, anthranilic acid and indoleacetic acid, and free radical reaction suppressor free fatty acids. Transcriptomic analysis suggested that the key gene involved in tryptophan metabolism, coinciding with the lipid metabolic processes and ion transports were most up-regulated in ΔNRPS under stress. Our results confirmed a lipid-mediated fungal response to cold stress and unveiled a link of tryptophan-based metabolic reprogramming to the fungal cold adaption.
The mechanism by which organisms respond to temperature changes via biosynthesis of small-molecules remained largely cryptic. We reported that a class of tryptophan-derived natural products via non-ribosomal peptide synthase (NRPS) pathway, prenyl indole alkaloids (PIAs), accompanied the lipid formation in thermophilic fungus T. dupontii under cold stress. PIAs deletion increased Fe3+ level and initiated tryptophan metabolism to yield lipid inhibitors and reactive oxygen species (ROS) suppressors. Concurrently, a large amount of unsaturated and saturated free fatty acids with free radical scavenging ability were also accumulated. Our findings confirmed that lipid mass under cold stress should be an inevitably boosting risk for the fungus and unveiled two alternative metabolite-lipid-cold relationships, which provided a new insight into the ecological and biological functions of tryptophan-associated metabolites. [Display omitted]
•Thermophilic fungus T. dupontii under cold stress accumulated lipid and tryptophan-derived metabolites, prenyl indole alkaloids (PIAs).•PIAs deletion under cold stress caused increased Fe3+ level but decreased lipid level.•Lipid inhibitor indole acid and ROS scavenger kynurenamines were accumulated in the mutant without PIAs.•Concurrently, free fatty acids including unsaturated ones, were accumulated in the mutant without PIAs under cold stress.•The most up-regulated gene in the mutant without PIAs under cold stress was responsible for the first step from tryptophan to kynurenamines.