Microbial activity metabolites

Microbial activity may produce reactive intermediates that undergo spontaneous chemical transformation to terminal metabolites. This is quite a frequent occurrence, and its diversity is illustrated by the following examples ... 

A series of soil microcosms were used to study the biodegradation and bioavailability of pyrene during long-term incubation. The nonextractable fraction of -labeled pyrene that had been introduced into pristine soil and incubated with or without the addition of azide was substantially greater in the latter (Guthrie and Pfaender 1998). It was also shown that microbial activity produced a number of unidentified polar metabolites that might plausibly be involved in the association. 

There has been considerable interest in the use of plants for bioremediation and this merits a rather extensive discussion. Plants can play an important role in bioremediation for several reasons (1) they can transport contaminants from the soil, (2) they can metabolize the contaminants after uptake, or (3) they can produce exudes that support microbial activity for degradation of the contaminants. In addition, bacteria can produce metabolites that counter the effect of toxins produced by fungi, and serve as biocontrol agents that diminish the need for the application of agrochemicals. Plant exudates play an important role in supporting the growth and activity of bacteria that carry out the degradation of contaminants in the rhizosphere and rhizoplane (the external surface of roots... 

Zhang, D., Hanson, R., Roongta, V. et al. (2006) In vitro and in vivo metabolism of a gamma-secretase inhibitor BMS-299897 and generation of active metabolites in milligram quantities with a microbial bioreactor. Current Drug Metabolism, 7, 883-896. 

Microbial activity can also be stimulated by mineral colloids through their ability to sorb metabolites that would otherwise have an adverse effect on microbial growth (Filip et al. 1972 Filip and Hattori 1984) This may be due to the toxicity of metabolites, and their feed back repression and, encouraging competitors. Predictably, montmorillonite (CEC —100 cmol kg-1 and specific surface of 800 m g 1) is more effective than kaolinite and finely ground quarts. Other substances, such as antibiotics and pesticides that are toxic to some microorganisms, can also be adsorbed by the surfaces of mineral colloids (Theng and Orchard 1995 Dec et al. 2002). 

To elucidate the fate of these compounds at sediment-water interfaces, sediment/water mixtures (Lake Macatawa, Holland, MI) were spiked with DCB and incubated at 20 °C for 12 months under anaerobic conditions [72]. Dehalogenation of DCB to benzidine appeared to take place through a transient intermediate, 3-monochlorobenzidine (Fig. 27), which was observed in time-course analyses of the sediment/water mixtures. No metabolites were observed in autoclaved samples, suggesting that dehalogenation of DCB in anaerobic sediment/water systems was mediated by microbial activity. The product of dehalogenation (benzidine, Fig. 27) is more toxic to humans than the parent compound, DCB. From sediment/water distribution experiments, DCB showed greater affinity for the sediment phase than its non-chlorinated derivative,... 

Cresols are widely distributed natural compounds. As discussed above, they are formed as metabolites of microbial activity and are excreted in the urine of mammals (Fiege and Bayer 1987) and humans (Needham et al. 1984). Cresols from human urine are probably biodegraded at municipal sewage treatment facilities prior to release to ambient waters. However, for combined septic and storm sewage systems, cresols may be released to surface waters during periods of precipitation when influent volumes exceed treatment plant capacities. Also, in rural and suburban areas where septic tanks are used (o- and m-cresols can resist anaerobic digestion), human excrement may be a nonpoint source release of cresols to groundwater. 

As discussed above, cresols are widely distributed natural compounds. They are formed as metabolites of microbial activity and are excreted in the urine of mammals. Various plant lipid constituents, including many oils, contain cresols. Cresols have also been detected in certain foods and beverages such as tomatoes, tomato ketchup, cooked asparagus, various cheeses, butter, oil, red wine, distilled spirits, raw and roasted coffee, black tea, smoked foods, tobacco, and tobacco smoke (Fiege and Bayer 1987). However, very few monitoring data for cresols in food were found in the literature. 

Low Molecular Weight Enzyme Inhibitors - Microbial Secondary Metabolites with Various Pharmacological Activity... 

It has been suggested that microbial cata holism of off-flavor metabolites may be enhanced to provide an effective method ) control off-flavors. Indeed, microbial cultures have been reported to degrade relatively high levels of off-flavor metabolites (53, 54, 55), but whether microbial activity can be used practically to improve the flavor quality of aquaculture systems remains to be determined. 

Residual concentrations of aminocarb in water as well as in sediment were higher in autoclaved samples because of the absence of microbial activity. The pattern of mobility of the chemical from water to sediment was similar to that observed in non-auto-claved samples, but its overall persistence was higher and because of this, a gradual buildup of the active ingredient in sediment occurred in the closed flask. Most of the aminocarb was likely adsorbed onto particulate matter in suspension and then gradually settled in the sediment. Nearly 97% of the fortified aminocarb remained in the autoclaved sample (closed flask) at the end of experiment out of this 34% was in water and 63% was adsorbed onto sediment. In contrast, 51% of the fortified amount of aminocarb remained in the open flask, of which 26% was in water and the rest in sediment. Sediments, like water, contained detectable levels of demethylated aminocarb moieties as well as the phenol, but among them, the monodemethylated derivative (methylamino Matacil) was predominant compared to the other two metabolites. 

Carolyn et al. have reported two additional ultraviolet-absorbing metabolites in urine specimens [12]. The drug is partially metabolized in the liver by modification of the piperazinyl group. Oxo-ciprofloxacin and tV-acetyl-ciprofloxacin microbial activities are comparable to norfloxacin, and desethylene-ciprofloxacin is comparable to nalidixic acid for certain organisms. About 40-50% of an oral dose is excreted unchanged in the urine, and 15% as metabolites. Upto 70% of a parental dose may be excreted unchanged, and 10% as metabolites within 24 h [13, 14]. 

To continue the successful discovery of biologically active metabolites from microbial sources, new approaches must be taken in order to reduce the probability of rediscovering known compounds. In this regard rare actino-mycetes and so-called uncultivable (or unculturable) actinomycetes represent a promising source of novel pharmacologically active compounds. 

Microbial Secondary Metabolites with Unique Biological Activity and Chemical Diversity... 

---