Secondary metabolites microbial synthesis

Many attempts have been made to find cholesterol biosynthesis inhibitors for development as hypocholesterolemic agents. Microbial secondary metabolites have been used as valuable natural sources in the development of novel cholesterol biosynthesis inhibitors. Mevastatin and lovastatin were isolated from the fungi, Penicillium citrinum and Aspergillus terreus, respectively, as potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which is involved in the rate-limiting step of cholesterol synthesis in mammals. These findings have led to the development of statins , which are drugs of choice in the treatment of hypercholesterolemia. 

Among the worldwide total of 30000 known natural products, about 80% stems from plant resources. The number of known chemical structures of plant secondary metabolites is four times the number of known microbial secondary metabolites. Plant secondary metabolites are widely used as valuable medicines (such as paclitaxel, vinblastine, camptothecin, ginsenosides, and artemisinin), food additives, flavors, spices (such as rose oil, vanillin), pigments (such as Sin red and anthocyanins), cosmetics (such as aloe polysaccharides), and bio-pesticides (such as pyrethrins). Currently, a quarter of all prescribed pharmaceuticals compounds in industrialized countries are directly or indirectly derived from plants, or via semi-synthesis. Furthermore, 11% of the 252 drugs considered as basic and essential by the WHO are exclusively derived from plants. According to their biosynthetic pathways, secondary metabolites are usually classified into three large molecule families phenolics, terpenes, and steroids. Some known plant-derived pharmaceuticals are shown in Table 6.1. 

It is expected that the biosynthetic capacity of plants could be exploited in vitro using plant cells and cell tissue systems, analogous to microbial cells in fermentation processes. An important requirement for the improvement of secondary metabolite synthesis is an understanding of the metabolic pathways and the enzymology of the biosynthesis of particular products. The knowledge of plant metabolic pathways is still very limited. It needs more in-depth study by biologists, which will help to make the chemical bioengineering more practical. 

Microbial de novo Synthesis of Plant Secondary Metabolites and Transgenic Plants... 

Occasionally the synthesis of a microbial product, for example that of ethanol from glucose, is catalysed by non-viable cells (section 6.2.1.1). Then the process is properly catalytic because the Saccharomyces cerevisiae cells do not change, for a time at least. However there are some industrially important reactions in which micro-organisms are first grown to a high biomass and are then added to a substrate which is almost quantitatively converted to a product. These are effectively catalytic processes in which one or a few enzymes in the organism transform an added substrate into a useful product. These transformations are divorced from cell growth, in contrast to syntheses such as those in which carbohydrates are converted into citric acid or complex feedstocks into secondary metabolites. 

Phytoalexins are low molecular weight products which are produced in response to elicitors such as microbial, herbivorous or environmental stimuli (Poulev et al. 2003). Once plants detect a pathogen signal, a complex mixture of secondary metabolites is produced to control the invader. These molecules are synthesized de novo, and thus involve the activation of certain genes and enzymes required for their synthesis (Kuc 1995). Phytoalexins are chemically diverse and may include many chemical classes such as simple phenylpropanoid derivatives, alkaloids, gly-costeroids, flavonoids, isoflavonoids, various sulphur products, terpenes and polyketides (Hammerschmidt 1999). There is no boundary between phytoalexins and phytoanticipins, and in one plant species a certain chemical can function as a phytoalexin, whereas it has the function of a phytoanticipin in another species (Junghanns et al. 1998). It is important to point out that the distinction between phytoanticipins and phytoalexins is not based on their chenucal structure but rather on how they are produced. Thus, the same chemical may serve as both phytoalexin and phytoanticipin, even in the same plant (VanEtten et al. 1994). 

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