Abstract
Lichens are a natural source of bioactive compounds. Cladonia metacorallifera var. reagens KoLRI002260 is a rare lichen known to produce phenolic compounds, such as rhodocladonic, thamnolic, and didymic acids. However, these metabolites have not been detected in isolated mycobionts. We investigated the effects of six carbon sources on metabolite biosynthesis in the C. metacorallifera mycobiont. Red pigments appeared only in Lilly and Barnett’s media with fructose at 15 °C after 3 weeks of culture and decreased after 6 weeks. We purified these red pigments using preparative-scale high performance liquid chromatography and analyzed them via nuclear magnetic resonance. Results indicated that 1% fructose-induced cristazarin and 6-methylcristazarin production under light conditions. In total, 27 out of 30 putative polyketide synthase genes were differentially expressed after 3 weeks of culture, implying that these genes may be required for cristazarin production in C. metacorallifera. Moreover, the white collar genes Cmwc-1 and Cmwc-2 were highly upregulated at all times under light conditions, indicating a possible correlation between cristazarin production and gene expression. The cancer cell lines AGS, CT26, and B16F1 were sensitive to cristazarin, with IC50 values of 18.2, 26.1, and 30.9 μg/mL, respectively, which highlights the value of cristazarin. Overall, our results suggest that 1% fructose under light conditions is required for cristazarin production by C. metacorallifera mycobionts, and cristazarin could be a good bioactive compound.
Highlights
Lichens are symbiotic organisms composed of a lichen-forming fungus and an alga, a cyanobacterium, or both
While the precise causal factors are unknown, it is expected that differences in nutrient conditions, especially carbon sources, account for changes in the polyketide biosynthesis pathway, which lead to differences in secondary metabolite profiles [7]
We discovered that the C. metacorallifera mycobiont produces cristazarin on a medium supplemented with 1% fructose
Summary
Lichens are symbiotic organisms composed of a lichen-forming fungus (the mycobiont) and an alga, a cyanobacterium, or both (the photobiont). Lichens produce various characteristic secondary metabolites, such as depsides, depsidones, dibenzofurans, pulvinates, chromones, and quinones. These metabolites, which have been detected in extracts of lichen thalli, are produced when isolated mycobionts are cultured without their algal partners [1,2,3,4]. Some mycobiont isolates cannot produce the metabolites that are detected in their symbiotic lichen form [5,6]. The secondary metabolite productions in various lichens with different carbohydrate carbon sources have been compared [8,9,10,11]. Lichen mycobionts have been reported to produce secondary metabolites in culture media supplemented with
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