The Source of “Fairy Rings”: 2‐Azahypoxanthine and its Metabolite Found in a Novel Purine Metabolic Pathway in Plants

Abstract

Rings or arcs of fungus-stimulated plant growth occur worldwide; these are commonly referred to as "fairy rings". In 2010, we discovered 2-azahypoxanthine (AHX), a compound responsible for the fairy-ring phenomenon caused by fungus; AHX stimulated the growth of all the plants tested. Herein, we reveal the isolation and structure determination of a common metabolite of AHX in plants, 2-aza-8-oxohypoxanthine (AOH). AHX is chemically synthesized from 5-aminoimidazole-4-carboxamide (AICA), and AHX can be converted into AOH by xanthine oxidase. AICA is one of the members of the purine metabolic pathway in animals, plants, and microorganisms. However, further metabolism of AICA remains elusive. Based on these results and facts, we hypothesized that plants themselves produce AHX and AOH through a pathway similar to the chemical synthesis. Herein, we demonstrate the existence of endogenous AHX and AOH and a novel purine pathway to produce them in plants.

Integrated analysis of transcriptome and metabolome of Arabidopsis albino or pale green mutants with disrupted nuclear-encoded chloroplast proteins

“…AHX chemically synthesizes from 5-aminoimidazole-4-carboxamide (AICA), and AICA is one of the members of the purine metabolic pathway. AHX and its metabolite (2-aza-8-oxohypoxanthine) are thought to be produced by plants themselves through a pathway similar to chemical synthesis (Choi et al 2010; Choi et al 2014). They stimulate plant growth (Choi et al 2014; Tobina et al 2014) and give environmental tolerance (unpublished data).…”

“…AHX and its metabolite (2-aza-8-oxohypoxanthine) are thought to be produced by plants themselves through a pathway similar to chemical synthesis (Choi et al 2010; Choi et al 2014). They stimulate plant growth (Choi et al 2014; Tobina et al 2014) and give environmental tolerance (unpublished data). Moreover, the purine metabolite allantoin enhances abiotic stress tolerance (Watanabe et al 2014).…”

High-Quality Draft Genome Sequence of Burkholderia contaminans CH-1, a Gram-Negative Bacterium That Metabolizes 2-Azahypoxanthine, a Plant Growth-Regulating Compound

“…The proteins encoded by the CH-1 genome were additionally annotated using BlastKOALA (12) to characterize protein functions and reconstruct the purine metabolism pathway in the KEGG database (13). Among 8,065 proteins, 82 were assigned to the purine metabolism pathway (ko00230), including the xanthine dehydrogenase small subunit (XdhA, K13481) and large subunit (XdhB, K13482), which are possibly involved in the conversion of AHX to AOH, as predicted by the purine metabolism pathway in plants (14). In addition, three proteins were assigned to the xanthine dehydrogenase accessory factor (XdhC, K07402), which is required for xanthine dehydrogenase activity in Rhodobacter capsulatus (15).…”

Effects of 2-azahypoxanthine on extracellular terpene accumulations by the green microalga Botryococcus braunii, race B

“…Thus, it seems that tri-and tetraterpene accumulations 73 areinversely coordinated with algal growth stages in B. braunii, although the underlying 74 mechanisms for this phonomenon is still largely unknown.To understand such regulatory 75 mechanisms for terpene biosynthesis in this alga,phytohoromone-likecompounds that affect growth 76 or terpene production could be good experimental tools. 77 A recently discovered bioactive natural compound, 2-azahypoxanthine (AHX) has garnered 78 considerable research interest as it has an ability to stimulate growth of crop plants and increasetheir 79 yields [20][21][22].It was originally identified from a fungus, Lepistasordida, as the compound 80 responsible for the formation of "Fairy rings", the phenomenon in which a ring of fungi causes nearby plantsto grow rapidly [20].In a more recent study, AHX and its oxidized derivative, 2-aza-8oxohypoxanthine (AOH), were also isolated from diverse plant species including green algae [23].…”

“…It was proposed that AHX is synthesized in vivo from the intermediate of the purine metabolism pathway, 5-aminoimidazole-4-carboxamide (AICA) [23], and subsequently oxidized to AOH, suggesting that AHXand its metabolites arewidely conserved bioactive compounds among plants( Fig. 3).Although the overall picture of this signaling pathway at the molecular level is still to be elucidated, its diverse effects on higher plants, from affecting ammonium uptake ability in root of rice [20] to stimulating carotenoid accumulation in juice sacof citrus,have alreadybeen described [24].…”