Secondary metabolisms polyketides

Tkacz JS, Polyketide and peptide products of endophytic fungi Variations on two biosynthetic themes of secondary metabolism, in Bacon CW, White JF, Jr (eds.), Microbial Endophytes Marcel Dekker, Inc., New York, NY, pp. 263—294, 2000. 

Overall, however, the immensity of temperate land corresponds to a most various secondary metabolic production, different from that of tropical land. The most renowned alkaloids belong to the morphine class (Chart 6.2.A1), and, in combination with isoprenoids, to the ergot and triterpene classes (Chart 6.2. A2). Prominent in the peptides are the cyclosporins (the first of which was isolated from a fiingus collected in Norway), streptogramins, and P-lactams (Chart 6.2.P). The isoprenoids are represented by pyrethrin monoterpenes, cedrane sesquiterpenes, ginkgolide and taxane diterpenes, ophiobolane sesterterpenes, and arborane and amyrin-like triterpenes (Chart 6.2.1). In the polyketides, epothilones, recently discovered from Myxobacteria, and the long known rapamycin, are two prominent classes of macrolides (Chart 6.2.FA/PO/C). 

Despite the thousands of secondary metabolites made by microorganisms, they are synthesized from only a few key precursors in pathways that comprise a relatively small number of reactions and which branch off from primary metabolism at a limited number of points. Acetyl-CoA and propionyl-CoA are the most important precursors in secondary metabolism, leading to polyketides, terpenes, steroids, and metabolites derived from fatty acids. Other secondary metabolites are derived from intermediates of the shikimic acid pathway, the tricarboxylic acid cycle, and from amino acids. The regulation of the biosynthesis of secondary metabolites is similar to that of the primary processes, involving induction, feedback regulation, and catabolite repression [6]. 

CPs are integral components of various primary and secondary metabolic pathways, including fatty acid synthesis (FAS), nonribosomal peptide synthesis (NRPS), polyketide synthesis (PKS), and lysine biosynthesis. All CPs harbor... 

Some of the functions of the S. coelicolor CYPs are in secondary metabolism operons, for example, CYP158A2 located downstream of a Type III polyketide synthase and CYP105N1 located downstream of a nonribosomal peptide synthase. These are currently subject to functional studies using the tools of gene disruption and metabolite/metabolome profiling, although not all the secondary metabolite genes identified... 

These same features appear to be responsible for creating diversity in other secondary metabolic pathways. For example, in both polyketide and teipene formation, repetitive addition of either C2 or C5 carbon subunits leads to the formation of a variety of carbon skeletons. In addition, in nearly all groups of secondary metabolites, including alkaloids, phenylpropanoids, and terpenes, the initially-formed products are subjected to a wide variety of oxidative modifications. Thus, despite the seemingly large and chaotic assemblage of secondary metabolites found in plants, their formation may he governed by a few common principles. 

Natural products often seem to have little value to the organism itself, and are made by the processes of secondary metabolism. They are classified by the way they are made into terpenes and steroids, alkaloids, and polyketides. 

Hopwcxxl DA, Khosia C. Genes for polyketide secondary metabolic pathways in microorganisms and plants. Chadwick DJ, Whelan J, eds. Secondary Metabolites Their Function and Evolution, Ciba Foundation Symposium 171- Chichester, England John Wiley and Sons. 1992 88-112. 

Covalent binding of precursors and intermediates to enzyme proteins brings about a most efficient form of channeling. In secondary metabolism, this has been shown for the biosynthesis of peptide antibiotics and polyketides (Table 3). 

The present book is the second of two volumes that provide state of the art expert reviews of central topics in modern natural products chemistry and secondary metabolism. Using specific examples, the previous volume emphasized two revolutions in experimental techniques that completely transformed the field of natural products chemistry from what it was in the 1950s. These were the use of stable isotopes in conjunction with modern NMR and mass spectrometry, and more recently, the development of molecular biological techniques to identify, purify and manipulate the enzymes responsible for the intricate series of steps to complex natural compounds. The previous volume specifically covered the use of isotopes in biosynthetic research and the formation of enzyme cofactors, vitamin B12 and reduced polyketides. 

Such complexes include fatty acid synthases (FASes), elongases (ELSes) and polyketide synthases (PKSes) which can fimction individually or in concert. FAS synthesizes the 16 and 18 carbon acyl chains of membrane lipids as well as those of the plant cutin and suberin monomers. ELSes use these acyl chains as primers to synthesize longer ones for storage lipids in some seeds and for cuticular and epicuticular waxes. PKSes participate in a wide range of secondary metabolic pathways. In plants chalcone synthase contributes to the carbon skeleton of the flavonoids, in fungi and bacteria, especially... 

It is evident that the aflatoxins, which are secondary metabolites par excellence, not only significantly contributed to the present comprehension of chemical carcinogenesis, but led to a better understanding of secondary metabolism, particularly polyketide biosynthesis. 

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