Description:
- Biosynthesis of natural products
- Elucidating cryptic biosynthesis pathways
Abstract
USC researchers set out to devise a biosynthetic gene clusters (BGC) refactoring strategy and heterologous expression platform in A. nidulans based on the afo regulon. Taking advantage of the transcriptional regulatory elements of afo, the afo genes were replaced with gene of interest from a target BGC, allowing the production of the encoded molecule. The researchers applied the platform to two high-value NP clusters and successfully engineered “microbial factory” strains that produce high-value fungal NPs with high yield and high purity.
The versatility and robustness of this method was demonstrated with the NPs citreoviridin, mutilin, and pleuromutilin.
The platform also allows the elucidation of cryptic biosynthesis pathways which can aid the identification of druggable targets.
Benefit
- Biosynthetic platform for the production of fungal natural products
- Fungal natural products accessible in high yield and purity
- Platform also useful for drug target identification through the elucidation of cryptic biosynthesis pathways
Market Application
Fungal natural products (NPs) are invaluable sources of new leads for the pharmaceutical and agricultural industries. However, the yields of fungal NPs from native producers are usually low, and total synthesis of structurally complex NPs is challenging. As a result, the commercialization is hindered by the cost of the production.
Publications
ACS Synthetic Biology 2021 10 (1), 173-182
Other
IP Status: patent pending
Stage of Development:
- Tested in vitro
- POC demonstrated with biosynthesis of 3 NPs
- Available for exclusive license