Microbial natural products are small molecules synthesized by bacteria or fungi, or produced from their components. These products have been hugely commercially successful in a variety of therapeutic areas. In practice, they are produced by scalable fermentation, followed by purification to homogeneity.
They have evolved to bind and interact with target molecules in biological environments. As such, they are enriched in phenotypic screens and represent an excellent starting point for drug discovery research.
Natural products continue to make a significant impact on the pharmaceutical industry. From 1981 to date, 79 (80%) out of 99 small molecule anticancer drugs are natural product-based/inspired, with 53 (53%) being either natural products or derived therefrom. Among the 20 approved small molecule New Chemical Entities (NCEs) in 2010, half of them are natural products.
Through evolution in a competitive environment or, as in the case of gut microbiota, through co-evolution with the human host, microbial natural products have several intrinsic properties favoring their consideration in drug discovery and development. Microbial natural products:
- Can be produced by large-scale fermentation
- Cover a diverse, relatively untapped chemical space
- One of few chemistries able to interfere with protein-protein interactions
- Microbial natural product analogues can be produced by metabolic pathway engineering
The advantage of Zylacta’s drug discovery process is the early evaluation of safety and efficacy of prototype compounds in humans. By concentrating on GRAS microbes such as probiotic bacteria, unpurified active compounds prepared from them can be administered to patients as functional food without FDA approval under the supervision of a physician. This approach provides confidence in the compound’s safety and efficacy very early in the drug development process.
Zylacta is currently one of a very few companies offering both its biosynthetic engineering and synthetic biology technologies, along with semi-synthetic chemistry to optimize natural products as a service.
We have significant experience in using this combination of techniques to optimize the properties of the molecule of interest to generate novel and inventive candidate drugs in a way that semi-synthesis alone cannot.