There is a perpetual demand for new drugs to provide better therapeutic outcome or overcome emerging drug resistance. While combinatorial chemistry approaches with pharmacophore fragments still await sophistication to fulfil high expectations towards lead discovery, using the structural diversity of natural products will greatly expand the chemical search space of traditional compound libraries. Furthermore, greater than a third of recently approved medicines are natural products or have been derived from lead compounds found in living organisms. Products derived from natural organisms are more likely to appeal to the ecologically conscious customers, especially in the food and personal care sectors. In addition, natural products are often perceived as being safer than chemically synthesized compounds. The A*STAR Natural Product Library (NPL) with ~160,000 plant, fungal and bacterial specimens, one of the largest in the world (Figure 1), is a prime resource partner for academia, industry and government research organizations who are looking for natural active ingredients.
This NPL has been developed over the past ~20 years through collection from targeted local habitats, diverse international collaborations and by strategic acquisitions. The genetic diversity within NPL is exceptional. With 57% of all known cultured fungal genera, over 67% of the world’s plant families and 70% of filamentous bacterial genera represented, the collection has been described as “the most diverse and comprehensive collection of plant and microbial samples in the world” (Prof Geoffrey A. Cordell, University of Illinois). In 2014, the Bioinformatics Institute was entrusted by the Agency for Science and Technology (A*STAR) to house the NPL previously acquired from MerLion Pharmaceuticals Pte Ltd. We do not only offer our collections of organisms, extracts and isolated natural compounds or the accompanying electronic databases. In contrast to NPLs elsewhere, we have an in-house Natural Product Discovery Platform (NPDP) that provides expertise in biological high-throughput screening (HTS), genomics, analytical chemistry, natural product research, synthetic
biology and bioinformatics. For mining the collection, we use (i) traditional biological HTS as well as alternative (ii) chemical, (iii) genomic and (iv) in silico screening approaches.
Biological Screening: Bioassay-guided compound isolation is accomplished through screening of the extracts against biochemical/cellular assays to identify biological activities of interest. Once the active extracts have been found, the active principles are purified using bioassayguided compound isolation. While HTS is thought to be entrenched with drug lead discovery and, perhaps, the agrochemical industry, it has not yet been as widely used in the food and consumer care space. The HTS team at BII has accumulated the experiences of around 200 screening campaigns, involving biochemical assays as well as microbial
and mammalian cellular assays. And 10% of the screens were for the discovery of bioactive ingredients for food and
consumer care applications. From these screening efforts we had isolated more than 2,000 bioactive compounds from
NPL (Figure 2A). Screenings can be carried out over the whole collection as well as over selected subsections such as plants, fungi or microbes from pre-defined habitats, with certain known usage such as edible plants or herbs and fungi used in Traditional Chinese Medicine. Our plant samples are usage-annotated (traditional and modern uses for the individual
plants and products derived thereof) and the information were collated from several web-based plant-related databases. Despite missing scientific evidence to support certain claims, such information offers an opportunity to target certain plants for further investigation. In our two recent screening campaigns using only the edible plants to search for natural functional ingredients for food application, we identified several active plants for our industry partners, and clinical trial is planned for one active plant, in preparation for product development.