Molecular secondary metabolites

Low-molecular-weight products, generally secondary metabolites such as alcohols, carboxyhc and an iino acids, antibiotics, and vitamins, can be recovered using many of the standard operations such as liquid-hquid extraction, adsorption and ion-exchange, described elsewhere in this handbook. Proteins require special attention, however, as they are sufficiently more complex, their function depending on the integrity of a delicate three-dimensional tertiaiy structure that can be disrupted if the protein is not handled correctly. For this reason, this section focuses primarily on protein separations. Cell separations, as a necessary part of the downstrean i processing sequence, are also covered. 

With remarkable accuracy, Democritus in the fifth century B.C. set the stage for modem chemistry. His atomic theory of matter, which he formulated without experimental verification, still stands, more or less intact, and encapsulates the profound truth that nature s stunning wealth boils down to atoms and molecules. As science uncovers the mysteries of the world around us, we stand ever more in awe of nature s ingenious molecular designs and biological systems nucleic acids, saccharides, proteins, and secondary metabolites are four classes of wondrous molecules that nature synthesizes with remarkable ease, and uses with admirable precision in the assembly and function of living systems. 

Very large Serine/Threonine kinases and the molecular Target of Rapamycin, a naturally occurring secondary metabolite, TOR proteins function within multiprotein complexes to couple cell growth and stress responses to environmental and developmental cues. 

C. Keel, U. Schnider, M. Maurhofer, C. Voisard, J. Laville, P. Burger, D. Ha,ss, and G. Defago, Suppression of root diseases by Pseudomonas fluorescens CHAO importance of the bacterial secondary metabolite 2,4-diaceiylphloroglucinol, Molecular Plant-Microbe Interactions 5 4 (1992). 

Intact bacteria were first introduced into a mass spectrometer for analysis of molecular biomarkers without processing and fractionation around 1975.6 The ionization techniques available at the time limited analysis to secondary metabolites that could be volatilized, such as quinines and diglycerides, and vigorous pyrolysis of bacteria was explored as an alternative.7 Although biomarkers were destroyed in pyrolysis strategies, computer-supported cluster analysis was developed to characterize pure samples. 

In 1977, a survey of low molecular weight sulphur-containing compounds in Nature ,4 noted that these secondary metabolites had little more in common than the possession of one or more sulfur atoms. The reader was left with a kaleidoscopic impression of almost 80 chemical structures. A comprehensive review today would require many hundreds of sulfur-containing chemical structures. 

Croteau R, Kutchan TM and Lewis NG. 2000. Natural products (Secondary metabolites). In Buchanan BB, Gruissem W, Jones RL, editors. Biochemistry and Molecular Biology of Plants. Somerset, NJ John Wiley Sons, pp. 1250-1318. 

Since 1988, the methods that we use to isolate cDNAs of alkaloid biosynthesis have become ever more facile and sensitive, allowing for more efficient cDNA identification. We do not, however, yet understand enough about the cellular localization of alkaloid formation or about the nature of the catalysts to move completely away from enzymology and biochemistry and to use only molecular genetic techniques to dissect these biosynthetic pathways. Even our most recently successful cDNA isolations and identifications involved classical protein purification. We are beginning now to use proteomics and EST sequencing to identify natural product biosynthetic cDNAs, but these approaches are more feasible when a specialized cell/tissue type in which secondary metabolite biosynthetic pathways are active, can be isolated and used as a protein or RNA source. 

Specificity of molecular bioactivity and differentially induced defenses are only two examples of factors that can confound the interpretation of patterns at the macroscale. As our knowledge of marine systems continues to expand, the relative abundance of secondary metabolites in different geographic locations may be better understood. However, the literature supports the idea that local pressures and habitat, genetic composition, mode of response and metabolism of the algae play a significant role in shaping distribution patterns of secondary metabolites (e.g. Wright... 

Alkaloids, nitrogen-containing compounds generally found as secondary metabolites in plants, are also classical examples of renewables. In contrast to terpenes, they show a great variety in molecular structure, and the different classes of alkaloids are usually based on their basic ring systems. Many pharmaceutically active... 

All organisms synthesize carbohydrates, lipids, proteins, and polynucleotides, although the details of their molecular structures can be somewhat species specific. These basic classes of macromolecules have changed little over geologic time. The secondary metabolites are more species specific and have also changed little over geologic time. Many are resistant to degradation, and those provide excellent biomarkers that have been preserved in ancient marine sediments and petroleum deposits. 

On the other hand, some compounds which are Included may not be true Gossypium secondary metabolites. Not only are the sources mentioned above possible contributors of exogenous compounds which have been Included in the accompanying Tables (I - X), but also it is quite possible that methods of isolation and analysis caused molecular transformation which created Isomers of true metabolites or even caused more drastic alterations. The diversity of structures which are plausible natural products is so great that it is not reasonable to exclude many of those reported simply on the basis of structure assignment. For this reason, it can be expected that some errors of inclusion have been made. 

Croteau RB et al (2000) Natural products (secondary metabolites). In Buchanan, B, Gruissem, W, Jones, R (eds) Biochemistry and molecular biology of plants. American Society of Plant Physiologists, Rockville, MD, pp. 1250-1268... 

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