Studies on the production of compounds and regulation of secondary metabolism by the cultures of isolated lichen mycobionts

地衣是由真菌、菌体和光合伙伴光生物组成的共生生物。在某些情况下，地衣真菌培养物在渗透胁迫条件下具有产生在地衣化状态下从未检测到的物质的能力。指出地衣分枝菌培养物可作为生物活性化合物的新来源。在培养地衣分枝菌的研究过程中，我们对日本地衣的分枝菌进行了培养，并对其代谢产物进行了研究。从葡萄球菌（Graphis spp.）培养物中分离出色素、苯醌类和甾醇类，从Lecanora spp.培养物中分离出苯并呋喃类、山酮类和脂肪羧酸类，从Pyrenula spp.培养的分枝菌中分离出多种异香豆素衍生物。13个新化合物的结构得到了阐明。通过向培养的Graphis、Lecanora和Pyrenula菌体中添加_<13> c标记的乙酸，验证了萘吡喃酮和山酮衍生物的纸箱骨架的生物成因，从培养的菌体中分离出许多从未在地衣化状态下检测到的多种代谢物，但在结构上与真菌毒素有关。可以推测，这些代谢物的代谢途径在地衣化前可以表达，但在相关地衣中由于它们对光生物的毒性而被抑制。在此背景下，我们研究了一些代谢物对一种光生物——翠鸟（Trebouxia erici）生长的影响，证明了一些代谢物对光生物的生长有抑制作用，而另一些代谢物则没有作用。一些分离的代谢物对癌细胞的抗增殖活性也进行了评价。

Lichens are symbiotic organisms comprised of a fungus, mycobiont, and a photosynthetic partner, photobiont. In some cases, cultures of lichen mycobionts have an ability under osmotically stressed conditions to produce substances which have never been detected in the lichenized state. It was pointed out that cultures of lichen mycobionts could be new sources of bioactive compounds. In the course of our studies on cultured lichen mycobionts, we cultivated mycobionts of the lichens collected in Japan and investigated their metabolites. From the cultures of Graphis spp., chromones, benzoquinones and a sterol were isolated, while benzofurans, xanthones and aliphatic carboxylic acids were isolated from those of Lecanora spp. From the cultured mycobionts, of Pyrenula spp., a variety of isocoumarin derivatives were obtained. The structures of thirteen new compounds were elucidated.The biogenetic origin of the carton skeleton in a naphthopyrone and xanthone derivatives was verified by feeding _<13>C-labeled acetate into the cultured mycobionts of Graphis, Lecanora and Pyrenula spp.A good many of diverse metabolites isolated from the cultured mycobionts have never been detected in the lichenized state but were structurally related to mycotoxins. It might be postulated that the metabolic pathways of these metabolites could be expressed for survival of the mycobiont in pre-lichenized condition, but suppressed in associated lichens because of their toxicity to photobiont. In this context, the effect of some metabolites on the growth of a photobiont, Trebouxia erici were studied to demonstrate that some metabolites inhibit the growth of the photobiont, but the other have no effect. The anti-proliferative activities of some isolated metabolites against a carcinoma cell line were also evaluated.