Bioactive natural products are a significant source of lead compounds for the development of clinically useful pharmaceuticals. Bio-prospecting is a valuable source of drug leads.
Two significant issues remain. Firstly, novel compounds with distinctive medicinally-useful properties must be found and secondly, the compound must be able to be made in large quantities.
Studying structure-activity relationships is a key tool to help solve these problems, as by isolating the active parts of a molecule, simpler analogues that can be synthesised at scale can be identified. Other developments could include culturing methods to activate 'cryptic' biosynthetic pathways as an alternative to increase supply or to yield analogue structures.
The bioactivity of any new compound is characterised using genome-wide profiling methods such as the yeast chemical genomics screen and other cell-based assays.
Microorganisms that exist in extreme ecosystems with temperatures up to 100°C are a very valuable resource for the discovery of novel natural products. To live in such conditions, the organism must develop a unique biochemistry, and that enables unique natural products to be made.
Extreme ecological niches, such as New Zealand's geothermal systems in the Taupo Volcanic Zone, are now seen as a source of unexplored microbial diversity, as they tend to select for novel microbial strains.
In a collaborative project with GNS Science, microbiologists have cultured many of these novel extremophilic strains and identified the first representative of a new bacterial phylum.
Bacteria are a renewable source of bioactives, readily cultivated even at industrial scales. Genetic engineering allows their biosynthetic machinery to be expressed in other hosts that are more amenable to large-scale culture, in less extreme conditions that are difficult and costly to reproduce on a large scale.
New Zealand Sauvignon Blanc wine is renowned world-wide. To understand wine flavour and aroma, we must understand the volatile compounds that are responsible. Two classes of compound are important in Sauvignon Blanc—volatile sulphur compounds and methoxypyrazines.
Volatile sulphur compounds
The sulphur compounds give the wine its distinctive passionfruit and gooseberry aromas. Understanding the biological and environmental factors that dictate the levels of these compounds requires highly accurate and sensitive analytical techniques.
Current methods use highly toxic organomercury extraction to concentrate the compounds prior to gas chromatography-mass spectrometry (GCMS) analysis. The significant human and environmental health risks associated with this technology make it outdated and dangerous. With our collaborator, Dr Richard Tilley, we are developing new, non-toxic and reliable methods for this analysis that will provide a cost-effective and safe alternative to the organomercury technique.
Pernod-Ricard New Zealand, owners of Brancott Estate (formerly Montana Wines) has helped supply materials for this project and offered industry placements for students to test and utilise the technology in the future.
Improvements to the understanding of the chemistry of both these compounds will enable the development of methods to control their concentration. This will equip grape growers and wine makers to design specific flavour and aroma profiles to target specific export markets.
Methoxypyrazines are responsible for the green capsicum aroma in wine. Although parts of their biosynthetic routes have been studied, environmental factors are known to affect the process and are still poorly understood.
We are using photochemical studies to find out how methoxypyrazines are degraded, in collaboration with Dr Gerald Smith.