Alkaloids microorganisms

Figure 1 shows fhe molecular structures of some alkaloids that have been studied in recent years for their transformations through microorganisms. 

Table 1 shows examples of some of the microorganisms involved in different biotransformation processes [11]. The following sections cite some more recent examples of microbial transformation of biologically important compounds, especially alkaloids and nitrogen-containing compounds. 

Not surprisingly, peyote enjoyed a brief period of use as a cardiac tonic. Recently, one of its alkaloids, hordenine, has been credited with antiseptic action against a wide spectrum of microorganisms. 

Microorganisms, plants, and mammalian systems all contain enzymes capable of catalyzing chemical transformations with alkaloid substrates. Interesting and useful enzyme reactions that may occur with alkaloids include oxidations, reduc-... 

The concept of microbial models of mammalian metabolism was elaborated by Smith and Rosazza for just such a purpose (27-32). In principle, this concept recognizes the fact that microorganisms catalyze the same types of metabolic reactions as do mammals (32), and they accomplish these by using essentially the same type of enzymes (29). Useful biotransformation reactions common to microbial and mammalian systems include all of the known Phase I and Phase II metabolic reactions implied, including aromatic hydroxylation (accompanied by the NIH shift), N- and O-dealkylations, and glucuronide and sulfate conjugations of phenol to name but a few (27-34). All of these reactions have value in studies with the alkaloids. 

Smith and Rosazza have suggested that microbial transformation experiments could best be carried out by using a series of perhaps 10 metabolitically prodigious microorganisms as microbial models. Microorganisms for such work may be selected on the basis of considerable literature precedence for their abilities to catalyze the desired biotransformation reaction (i.e., O-dealkylation, N-dealkylation, aromatic hydroxylation, and reductions). The alkaloid substrate... 

All of the principles and ideas covered in the previous section may be translated directly to the use of microorganisms as tools in the production of compounds of plant biosynthetic or biodegradative importance. Just as one finds microbial systems to be of value in preparing metabolites in mammalian systems, it may be possible to use microbial transformations to prepare derivatives of alkaloids that might be found rarely or only in very small quantities in plants. In this way, abundant prototype alkaloids may be used as microbial transformation substrates to provide a range of metabolites. As in the mammalian case, metabolism studies using plant tissues, tissue cultures, or cell-free extracts may be conducted in parallel with microbial metabolic systems. Metabolites common to both would be prepared in quantity by relatively simple fermentation scale-up methods. 

The antitumor alkaloid ellipticine (5,1 l-dimethyl-6//-pyrido[4,3-b]carbazole) has been isolated from many species of Ochrosia and Aspidosperma. Ellipticine and its derivatives are highly active versus several experimental neoplasms, and the compound has been widely subjected to studies devoted to its total synthesis, the preparation of derivatives, and metabolism. Metabolic transformation studies with ellipticines have been conducted, using microorganisms, in vivo and in vitro... 

Microbial transformations of four heteroyohimbine stereoisomers [ajmalicine (81a) tetrahydroalstonine (81b), isoajmalicine (81c), and akumigine (81d)] yielded mixtures of 10- and 11-hydroxylation products (786) (Scheme 21). Microorganisms known for their abilities to metabolize indole alkaloids, steroids, and antibiotics were intitially screened, and seven cultures were further used for preparative-scale incubations with alkaloid substrate. The microorganisms used and yields (by HPLC) of metabolites obtained from 81a-81d are shown in Table HI. 

Nearly all of the microbial and mammalian transformation studies with this group of alkaloids have been focused on nicotine. Microorganisms have been used to resolve racemic nicotine to make available unnatural (/ )-(+)-nicotine for biological evaluation. Highly significant work has detailed the mechanism of nicotine oxidation in mammals, and has resulted in the identification of reactive intermediates formed as the alkaloid is transformed by hepatic monooxygenases. The chemistry and pharmacology of the pyridine alkaloids is discussed by Strunz and Findlay in Volume 26 of this treatise. 

Table IV summarizes most of the information considered in this review of alkaloid transformations and considers the alkaloids studied, the reactions observed and described, and the biocatalysts that accomplish biotransformation reaction. Only the generic names of microorganisms involved in alkaloid transformations have been given in this table, and the parentheses () contain the...

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