Daigo Wakana

New citrinin derivatives isolated from Penicillium citrinum

Three new coupling compounds derived from citrinin (9) and 2,3,4-trimethyl-5,7-dihydroxy-2,3-dihydrobenzofuran (8) – penicitrinone A (1), penicitrinolxa0A (2) and penicitrinonexa0B (3) – and a new citrinin derivative – decarboxydihydrocitrinin (4) – were isolated along with 3-methoxy-1-methyl-4(1H)-quinolone (5), quinolactacin A2 (6), dihydrocitrinone (7), 2,3,4-trimethyl-5,7-dihydroxy-2,3-dihydrobenzofuran (8), citrinin (9), quinocitrinin A or B (10), and decarboxydihydrocitrinone (11) from the extract of Penicillium citrinum IFM 53298. The relative structures of compoundsxa01–4 were confirmed on the basis of spectroscopic investigations and chemical correlations. Citrinin (9) and quinolactacin A2 (6) both showed antifungal activity.

A new indoloditerpene derivative, penijanthine A, isolated from Penicillium janthinellum

In a screen searching for new bioactive agents, a new indoloditerpene, penijanthine A (1), was isolated from Penicillium janthinellum IFM 55557. The structure of 1 was established on the basis of spectroscopic and chemical investigation, as well as detailed comparison with the spectroscopic and physico-chemical data of paxilline (2), which was isolated along with 1.

The cytotoxic and antifungal activities of two new sesquiterpenes, malfilanol A and B, derived from Malbranchea filamentosa

The cytotoxic and antifungal activities of two new sesquiterpenes, malfilanol A and B, derived from Malbranchea filamentosa

Structures of new triterpene glycosides, malbrancheosides A-D, from Malbranchea filamentosa

In the course of searching for new biologically active metabolites in Malbranchea filamentosa, four new triterpene glycosides, malbrancheosides A (1) - D (4), were isolated. The structures of 1- 4 were confirmed by the chemical and spectroscopic investigation. Malbrancheosides A (1) - D (4) are the first example of triterpenoidal glycosides having D-glucosamine derivatives from the fungal sources.

Isolation and identification of berberine and berberrubine metabolites by berberine-utilizing bacterium Rhodococcus sp. strain BD7100.

Based on the finding of a novel berberine (BBR)-utilizing bacterium, Rhodococcus sp. strain BD7100, we investigated the degradation of BBR and its analog berberrubine (BRU). Resting cells of BD7100 demethylenated BBR and BRU, yielding benzeneacetic acid analogs. Isolation of benzeneacetic acid analogs suggested that BD7100 degraded the isoquinoline ring of the protoberberine skeleton. This work represents the first report of cleavage of protoberberine skeleton by a microorganism. Graphical abstract BBR-utilizing bacterium, Rhodococcus sp. BD7100 demethylenated BBR and BRU, yielding benzeneacetic acid analogs in which their protoberberine skeletons were cleaved.

Production of an emericellin and its analogues as fungal biological responses for Shimbu-to extract

This research examined the production of fungal metabolites as a biological response to Kampo medicines. Shimbu-to (SMB) is a Kampo medicine composed of five herbal components: peony root (Shakuyaku), ginger (Shokyo), processed aconite root (Bushi), Poria sclerotium (Bukuryo), and Atractylodes lancea rhizomes (Sojutsu). High-performance liquid chromatography (HPLC) analysis of the fungus Aspergillus nidulans CBS 112.46 incubated in potato dextrose broth supplemented with SMB extract revealed emericellin (2) as the major peak and new xanthone analogues 24-hydroxyshamixanthone (1), shamixanthone (3), epishamixanthone (4), pre-shamixanthone (5), and variecoxanthone A (6) as minor peaks. The structure of 1 was determined by detailed analysis of 1D-NMR, 2D-NMR, and MS data. The results suggest that SMB extract regulates the biosynthesis of emericellin and its analogues in A. nidulans. Further investigations revealed that glucose induces the biosynthesis of emericellin and its analogues in A. nidulans in a concentration-dependent manner.

Common origin of methylenedioxy ring degradation and demethylation in bacteria

Plants produce many specific secondary metabolites as a response to environmental stress, especially biological stress. These compounds show strong biological activities and high stability against degradation by microbes and animals. Berberine, a benzylisoquinoline alkaloid, is found in many plant species and has strong antimicrobial activity, and is often included in traditional herbal medicines. We previously investigated how berberine is degraded in nature and we isolated two berberine-utilizing bacteria. In this study, we characterized the gene encoding the enzyme that degrades the 2,3-methylenedioxy ring of berberine; this ring is important for its activity and stability. Further characterization of several other berberine-utilizing bacteria and the genes encoding key demethylenation enzymes revealed that these enzymes are tetrahydrofolate dependent and similar to demethylation enzymes such as GcvT. Because the degradation of O-methyl groups or the methylenedioxy ring in phenolic compounds such as lignin, lignan and many other natural products, including berberine, is the key step for the catabolism of these compounds, our discovery reveals the common origin of the catabolism of these stable chemicals in bacteria.