Natural Products Laboratory, Institute of Biology, Leiden University

Natural products are still fascinating resource for many science fields but…

Natural products research provide incomparable source material to diverse fields of natural science such as drug development, ecology, metabolomics, or plant physiology. The huge number of chemicals have been considered as fascinating resource for the research fields. However, the chemical diversity of natural products and their large dynamics in concentration has been a big obstacle to make them ready for real utilization. Also, there are more difficulties for natural product research. Although natural products are treasure for new compounds the availability of the compounds are very limited due to the small quantity and very species specific (particularly secondary metabolites). Most of natural products are not commercialized, if any, the price is quite high for large use. Thus, many groups are trying to isolate interesting compounds for further use but even after the isolation the identification is not easy work because there are no reliable database for a broad range of natural products including secondary metabolites. In organisms most of quantity of chemicals come from primary metabolites like sugars, amino acids, and lipids which play essential physiological role for surviving. However, the diversity of chemicals definitely come form secondary metabolites including flavonoids, phenylpropanoids, terpenoids, alkaloids and so on. Despite the enormous diversity which is beneficial for the source of chemicals The availability of these secondary metabolites are dependent on the species, and growing and cultural condition. In these days many countries are trying to keep their biodiversity and consider their own organisms as valuable or profitable source. It makes it hard to supply proper amount of target natural products. Moreover, the yield of natural products are largely affected by environmental condition, e.g., seasonal or geographical variation. In the context many research groups have applied biotechnology in order to obtain stable amount independently from source species by manipulating genes. So far, a great effort has been performed for this subject but in the case of most secondary metabolites there are very few successful results because there are too many genes involved in the biosynthesis to be manipulated. For real application of natural products or investigation of their role in organisms large quantity of compounds are required. For instance, in drug development, kg level of the compounds are needed further bioactivity or clinical tests after a certain pre-screening test.
In order to solve the low quantity problem, regardless biotechnology approach, several classical approaches have been used. Using the isolated compound target chemicals have been chemically synthesized. Many examples have been reported as successful cases for the chemical synthesis. However, the cost has been thought as major problem with commercialization. Most natural products have many chiral centers which makes difficult to synthesize stereo-selectively. Large-scale extraction and isolation using diverse chemical engineering technologies have also been applied to produce higher yields of target compounds. As mentioned, raw materials have limitation for the maximum yield even though improvements are achieved.
Natural products are undoubtedly fascinating topic for many researches but their huge chemical diversity, low quantity, and limited availability for original resources are obstacles which should be solved by next generation of natural product research groups. In addition to these practical issues, there is one more basic questions left for further research topic of natural products, why organisms, particularly plants product such a diverse secondary metabolites?, what are the roles in organisms? We already know in a single plant species produce at least 3000 metabolites with very small quantity but we don’t know yet what exact roles of the compounds in organisms. For examples, in the case of flavonoids, any plant leaf or flower has own profile of the compounds. There are many hypothesis for the roles of flavonoids such as involving in plant defense mechanisms, UV protection, or relation to pollination. But none of them are clearly proved yet. Another examples are about saponins, why some plants produce so diverse sugar attached saponins as well as the position and numbers? Related to this topic of secondary metabolites, there is another basic question. If organisms produce a wide range metabolites, organisms require a media alternative to water or lipid because apparently most of secondary metabolites are soluble at all in water nor lipid.

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Natural Products Laboratory
Institute of Biology
Leiden University
Sylviusweg 72
2333 BE Leiden
The Netherlands

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