natural-products-in-plant-pest-management

274 S. HettiarachiIn an attempt to restore the ability to produce taxol, an anticancer drug,to an endophytic fungus, Tubercularia sp., mutagenesis and genome shufflingin protoplasts resulted in no restoration, but the production of new metabolites(Wang et al., 2010). One mutant produced three new and one alreadyknown sequiterpenoids, whereas another one made 18 novel compoundsbelonging to different classes and 10 already known compounds which werenot present in the wild-type strain.Altering the culture condition alone can induce the production of differentnatural products by an individual organism. If the mechanism of controlof a metabolic pathway is understood, then breaking silence in expressionshould be simple. Sometimes the presence of another organism in theneighbourhood may influence the induction of a pathway leading to a previouslyunseen product. Therefore mixed fermentation can result in anincreased concentration of already expressed or undetected or unexpressedmetabolites in crude extract, and the production of new analogues of knownmetabolites due to combined or extended pathways (Pettit, 2009).Each and every step of biochemical pathways are supposed be catalysedby a specific enzyme. Nevertheless, the size of the total genome, as unravelledby genome-sequencing projects, cannot account for the large number ofmetabolites present in organisms. Post-transcriptional modifications leadingto the formation of isozymes can be partly responsible for the high diversityof metabolites, but this has now been mainly attributed to the low specificityof some enzymes, which means that one enzyme can convert several similarprecursors or intermediates into several products causing ramifications inthe next step, and finally ending up with several end products. The numberof end products shall be much higher if there was no compartmentalizationof substrates and enzymes within a cell and in different cells. Bringing a naturalsubstrate in one cell in contact with an enzyme from another cell mayresult in entirely new ‘natural’ products. This is possible through breeding ofsexually compatible individuals, or through protoplast fusion, which is possiblebetween rather distant relatives. This technology is known as combinatorialbiosynthesis or metabolic engineering or heterologous expression, andhas been applied to microorganisms as well as to plants.Polyketides are highly diverse natural products, including those importantas antibiotics and other pharmaceuticals such as anticancer agents andimmunosuppressors. The most important producers are actinomycetes, butother bacteria, fungi, plants and marine animals also contain polyketides.They are formed by the sequential polymerization of carboxylic acids, and assuch carboxylic acid monomers become a source of variation in polyketides.The diversity has been possible due the modular nature of the polyketidesynthases (PKSs). Once transcribed, the peptides assemble to make the functionalenzyme consisting of different number of polypetides, each havingtwo modules. The large protein adds one monomer at each module to thegrowing chain. Mutagenesis in each module is possible and the outcome ofeach mutation and combinations of those can cause a great variety ofpolyketides (Kosla, 1997). The first polypeptide in the assembly of themegasynthase initiates polymerization and is the minimal PKS containing