Modern techniques and approaches in natural product chemistry and analysis

Objective: Review recent developments in natural product chemistry and analysis.

Key question: What efficiencies can these techniques offer?

Advancements in technologies are making it easier and more efficient to discover, analyse and use natural products. This reduces the environmental impact of discovery and production. Here are some key technologies helping progress in the field.

Green extraction technologies

Techniques like supercritical fluid extraction have greater efficiency in extracting natural products. Less energy, less solvent and less time are needed compared to traditional methods of extraction.

For example, supercritical fluid extraction using carbon dioxide (CO2) is widely used for extracting natural products such as essential oils e.g. eucalyptus oil, bioactive compounds, flavours and fragrances from natural products.

In supercritical CO2 extraction, the CO2 is brought to a supercritical state under high temperature and pressure. In this state, it has properties of both a gas and a liquid. It can penetrate plant materials like a gas and extract compounds from it like a liquid. The mixture of CO2 and dissolved compounds can be transferred for separation.

By reducing the pressure, the CO2 returns to gaseous form and evaporates leaving a high quality extract free of residual solvent contaminants. Moreover, the CO2 gas can be captured and recycled. CO2 is non-toxic and readily available, avoiding the need for more toxic solvents and the ability to recycle the CO2 make it more environmentally friendly.

Advances in cell culturing

Many types of organisms and cells can now be grown in bioreactor vessels in laboratory and factory settings, which is called “cell culturing”. Biologically active environments can be simulated and supported allowing us to use biotechnologies for the production of biological products and to perform biological processes. We have seen in previous sections how these technologies and the efficiencies they can offer can help meet supply demands, reducing pressure on species numbers in the wild, all at reduced cost.

Still further innovations are needed in culturing. Sometimes it is very difficult to culture organisms outside of their natural environment or sometimes organisms in culture will not produce the same range of compounds that they do in the natural environment. It is estimated that only 1% of microorganisms from the soil have been successfully cultured.

Soil bacteria naturally produce antibiotics as a competitive mechanism. When we consider that soil bacteria have been the natural source for the discovery of many of our antibiotics, it is clear that there is potential for future discovery of novel antibiotic molecules. When faced with the challenge as to why certain microbes do not grow well under laboratory conditions, scientists have developed cultivation methods to enable culturing in the natural environment.

Teixobactin is an antibacterial compound discovered in this manner. In 2014, scientists discovered a new species of bacteria, Eleftheria terrae, in a field in Maine using the isolation chip or iChip technique. The iChip is a small plastic block that allows a soil sample to be returned to the site the sample came from for incubation.

Special membranes allow nutrients and growth factors to reach the culture inside the iChip. This can lead to the growth and isolation of one species of microbe inside the iChip. Approximately 10,000 iChip cultures were screened in the project that discovered E. terrae from which Teixobactin was subsequently isolated.

Advances in Genome mining and engineering

Scientists can now decode and understand the genes involved in an organism’s metabolism. In some cases, a microbe’s metabolites and their functions can be predicted. Computational technology tools can mine huge amounts of genomic data to generate new knowledge. This has application in the identification of novel compounds in drug discovery and novel enzymes and bioactive compounds for industrial applications. Genetic engineering can manipulate these pathways to enhance production or even replicate them in a more easily cultivated organism.

Metabolomics

The metabolome is the complete set of metabolites or chemical fingerprint of a cell or organism and metabolomics is the study of these metabolite profiles. Complex mixtures, such as natural products, can be profiled comprehensively. Data mining and application of algorithms allows us to predict molecules responsible for bioactivity in a complex mixture and makes discovery of novel bioactive compounds easier. Metabolomics also has applications in quality control.

Through establishing a chemical fingerprint, producers can ensure consistency which is essential for product safety. Metabolomics can help us understand how genetic and environmental factors affect the metabolome allowing optimisation in growing and harvesting practices.

Machine learning and Artificial Intelligence

Machine learning and artificial intelligence can analyse large datasets to identify patterns and correlations to guide natural product discovery and predict biological activity and behaviour of natural products in the body.

These modern techniques and approaches in natural product research and development are enabling the discovery of novel compounds for a wide range of applications in the natural product sector.