Microbial Transformation of Rubijervine.

Abstract

Veratrum alkaloids are a group of potent hypotensive agents that act by reflex suppression of the cardiovascaular system. 2,3) Rubijervine (1) is one of the most common Veratrum alkaloids possessing the 22,26-epiminocholestane (solanidane) skeleton.4) The interest in Veratrum alkaloids has recently been renewed as they were patented several times during the past few years. [5][6][7][8] The use of steroidal alkaloids including solanidanes and C-nor-D-homosteroidal alkaloids to reverse or inhibit multidrug resistance in cancer or in bacterial, fungal, or parasite infections was reported. 5)The potent regulatory effects of jervane Veratrum alkaloids on hedgehog signaling, modulation of cholesterol biosynthesis and transport, and control of cell proliferation during mandibular arch morphogenesis have recently been reported. [6][7][8] Rubijervine and isorubijervine are suggested to be the plausible biogenetic precursors of cevanine and other C-nor-D-homosteroids. 9) Rubijervine is classified as a possible carcinogen for humans, based on its high tg a value when evaluated by the DC polarography method in anhydrous N, N-dimethylformamide. 10) The antimicrobial activity of rubijervine and other Veratrum alkaloids against Pityrosporum ovale, Trichophyton mentagrophytes, and Saccharomyces cerevisiae and against the basidiomycetes Polstictus versicolor has been reported. 11,12) Metabolism studies have been used successfully as model systems to predict metabolic pathways in humans or to increase the efficacy of drugs by metabolic activation. 13)Steroidal alkaloids have been investigated in metabolism studies due to their interesting biological activities.14) Tomatidine is a known spirosolane-type Solanum alkaloid related to rubijervine.15) Incubation of tomatidine with Nocardia restrictus, Mycobacterium phlei, and Gymnoascus reesii resulted in the metabolism of tomatidine to 1,4-tomatidien-3-one, tomatidone, tomatanin-3a-ol, 1-tomatiden-3-one, and 4-tomatiden-3-one but failed to induce any N-containing side chain modification.15) Solanidine (12-deoxyrubijervine) was the subject of a previous microbial metabolism study which enabled its conversion into 11a-hydroxysolanidine using the fungus Helicostylum piriforme ATCC 8992.16) The microbes Nocardia species ATCC 21145 and Cunninghamella elegans ATCC 9245 were able to metabolize rings A and B of the Cnor-D-homosteroidal Veratrum alkaloids veratramine and jervine, respectively, but failed to metabolize rings C and D or its N-containing side chain.17,18) Rubijervine (1) was chosen for a microbial bioconversion study in an attempt to prepare new analogues, to determine if there was any metabolism in the N-containing side chain, and to compare its metabolism with that of solanidine, tomatidine, veratramine, and jervine.Twenty-three growing cultures were screened for their ability to bioconvert 1. Only one culture (C. echinulata ATCC 9244) was observed to transform 1 completely to metabolites of greater polarity. Hence this microbe was chosen for preparative-scale fermentation be...

Microbial Transformation of Nitrogenous Compounds

“…4. The microbe C. echinulata ATCC 9244 was able to metabolize rings A and B of rubijervine but failed to metabolize rings C, D, or its N-containing side chain, a finding which is analogous to the results of previous fermentation studies of steroidal alkaloids [38].…”

“…Rubijervine is one of the most common Veratrum alkaloids possessing the 22,26-epiminocholestane (solanidane) skeleton [37]. The preparative-scale fermentation of rubijervine with Cunninghamella echinulata ATCC 9244 has been reported together with the resulting new metabolites 7α-hydroxyrubijervine and solanid-5-ene-3β,12α-diol-1-one [38]. The structures of rubijervine and its metabolites are shown in Fig.…”

“…In a recent publication, Wang and coworkers (2005) reported the "green" synthetic process of 6-hydroxy-3-succinoyl-pyridine from S-nicotine in to- 4 Structures of rubijervine and its metabolites [38] bacco waste utilizing whole cells of a Pseudomonas sp. [39].…”

Microbial community succession and toxic alkaloids change during fermentation of Huafeng Dan Yaomu

“…Fermentation is one such processing method. Micro-organisms play an important role in the fermentation process, which can transform chemical components (El Sayed and Dunbar 2002;Shibuya et al 2003). The microbiota may have led to these chemical changes.…”

Microbial Transformations of Plant Secondary Metabolites

“…Cunninghamella elegans 9245 transformed the C-nor-D-homosteroidal alkaloid jervine (Fig. 7), found in Veratrum plants, into jervinone as the major metabolite and additionally epimerized C-3 position producing 3-epi-jervine [134,135].…”