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Author(s): R Verpoorte

Email(s): VERPOORT@Chem.Leidenuniv.NL

Address: Natural Products Labratory, Institute of Hiology Leiden, Leiden University. PO Box 9505, 2RA Leiden. The Netherlands.

Published In:   Volume - 29,      Issue - 1,     Year - 2016

DOI:

ABSTRACT:
Life Sciences are going through a rapid change Since molecular biology started its advance some 30 years ago, it had a major landmark in obtaining the full secquence of the human genome, followed by that of various other organisms. We are now reaching the phase that the 1000 S full sequencing of an organism becomes reality It is almost cheaper to sequence again than to save the full sequence of an organism. At the same time it becomes clear that having a sequence does not help much to really understand a living organism. The high expectations for drug development, for example, have shown to be over optimistic, as so far no novel drugs have resulted from this knowledge. For natural products based drug development the trend was at-random screening of crude plant extracts. More recently a metabolomcs approach came into the picture as that helps in fast dereplication and also allows finding possible synergy and pro-drugs, which particularly is of interest in studying medicinal plants The importance of this systemic approach can be illustrated by the fact that plants can be considered to be super organisms in the sense that they are dependent on the collaboration of the plant with all kind of microorganisms, eg in the rhizosphere, but also endophytes in the plant itself. That means many new potential sources for leads for drug development, In the classical way plants were studied for single active compounds, often in a targeted approach. Particularly alkaloids were and are still a valuable resource for drug development. In fact about 80% of all known drugs do contain an amine function. In the natural product rescarch in the past there were specialists for each major class of natural products. Nowadays one needs to be a generalist and able to isolate and structure elucidate any compound from any source. However, that means that hasic knowledge about the different classes is disappearing. Particularly the open-access publication bype results in journals that are only interested in publishing many papers and not in having a high quality as the money comes from the authors and not from the readers, and consequently one may find quite surprising results being reported. With the rapid erosion of basic knowledge it might be worth to go against this trend and go back to a combination of basic knowledge on alkaloids and learning either from nature, ie plant interactions with its environment, or from our ancestors, Le. traditional medicines. The advancement in all the tools for isolation and structure elucidation of natural products with the understanding of alkaloid biosynthesis and metabolic engineering as important tools for ensuring future production, form an excellent basis to open a targeted approach for novel alkaloid leads for drug development.

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