Freddie Dudbridge and Steven Moss recently attended the SIMB conference ‘Natural Product Discovery and Development in the Genomic Era’.
This five-day event focused on current issues across natural product discovery, biocatalysis, enzyme mechanisms and genomic data with presentations from academia and industry. Here are what we picked out as the key themes and talking points from this conference.
Biocatalysis is an important, and improving, tool in sustainable chemistry.
Biocatalysis continues to mature, enabling this tool to be applied in an increasing number of transformations. Through protein engineering and directed evolution in combination with rational design strategies, it is possible to synthesize complex molecules using DNA-encoded biocatalysts.
Protein engineering leverages techniques such as gene synthesis and in vitro protein mutagenesis to allow for protein sequence optimization, while directed evolution mimics the power of natural selection towards protein optimization.
During the conference, one-pot multistep synthesis of APIs via biocatalysis was described. Other talks discussed engineering techniques that enable us to elaborate complex molecules without multiple protection groups – late-stage functionalisation (LSF).
Biocatalysis is a powerful tool that can be used to boost research and unlock the potential of future transforming technological advances. Discussions about biosynthesis and enzymology deepened our collective understanding of complicated biosynthetic pathways, as well as shedding light on novel enzyme workings.
Natural product discovery continues to deliver in drug discovery.
Natural product discovery is a vital addition to drug discovery and development, providing potentially useful starting points for potent drug molecules.
Current scientific research in this field is driven by advances in our understanding of biology, particularly genomics and synthetic biology. This has opened exciting possibilities for discovering previously hidden potential such as harvesting bacteria from extreme and previously untouched ecosystems or activating silent/cryptic biosynthetic gene clusters.
During the conference, the role of genome mining was set out as at the forefront of NP discovery. Through exploring bacterial or fungal resistance genes and other markers from unique sources such as the microbiome, computations and chemical techniques are being used to detect drug classes - unveiling gene clusters with newfound biochemical pathways.
Enzymology as a driver of innovation
As a community we continue to develop a mechanistic understanding of how natural products are assembled. This deeper understanding comes from increasing data and improved techniques.
Advancements in bioinformatics and protein-based databases now provide the opportunity for research laboratories to rapidly identify and characterize enzymes that are involved in a process, while being able to quickly create well-defined variations.
During the conference, enzyme engineering techniques that improved existing function and generated new activities were described; these in turn lead to accelerated process discovery, advancing product development, and allowing optimization studies at unprecedented speeds.
Bioinformatics and data science at the heart of drug discovery
Bioinformatics is one of the key technologies at the centre of drug discovery. Using bioinformatic techniques, genes associated with the biosynthesis of natural products can be identified. This opens up the potential for predicting structures of bioactive compounds before they are produced. Bioinformatic analysis enables researchers to find new proteins that have a similar function to ones already known or those with a novel function altogether.
The conference emphasized the use of bioinformatics to identify cryptic clusters and the activation of these clusters by manipulation of regulators and heterologous expression of the biosynthetic gene clusters. Further techniques to identify novel cluster included genome mining using a particular genomic signature such as a resistance gene. Methods of dereplication at the genome level were highlighted and transcriptomics used to help describe regulation.
The conference was a great success with many interesting talks and posters presented. The future of natural product discovery is exciting, with novel techniques being developed all the time to identify elusive natural products. Isomerase is at the forefront of this research and we are passionate about helping companies achieve their goals in this area. If you would like to chat with us about any aspect of your own natural product journey, please don't hesitate to get in touch (www.isomerase.co.uk).