Biomining drug-like small molecules from microorganisms
The Science and Technology behind Design Pharma
Microbial and plant specialized metabolites are key mediators of microbe-microbe and host-microbe interactions and constitute a rich resource for drug development. The research group of Design Pharma’s co-founder Marnix Medema develops and applies computational approaches to identify, classify, and prioritize specialized metabolite biosynthetic gene clusters and pathways and to connect them to specific molecules to allow a more comprehensive interpretation of the chemical language between hosts and microbes.
Design Pharma uses these powerful algorithms to identify biosynthetic gene clusters (BGC) and engineer these gene clusters for rapid synthesis of drug candidate molecules in vitro using its proprietary cell-free biosynthesis platform.
The bioinformatics pipeline involves the use of antiSMASH, which identifies biosynthetic gene clusters (BGCs) that are analyzed by BiG-SCAPE at large scale to construct a BGC similarity network and group them into gene cluster families (GCFs). Subsequently, CORASON-based multi-locus phylogenetic analysis is used to elucidate the evolutionary relationships of BGCs within each GCF, which facilitates the selection of enzymes for compound biosynthesis and a compounds’ chemical modification by tailoring enzymes.
The figure was published in Navarro-Munoz et al., Nature Chemical Biology 16, 60-68 (2020), co-authored by Marnix Medema.
This pipeline of software tools combines perfectly with Design Pharma's ability to rapidly build comprehensive cell banks of microorganisms for biomining genomes for drug discovery, as well as our unique cell-free biosynthesis platform to engineer and optimize biosynthetic gene clusters for the synthesis of drug candidates in vitro within weeks.
In our next post, we will describe how Design Pharma can rapidly access the vast diversity of the living microbiota for functional testing and genome mining.
Read?https://journals.asm.org/doi/epub/10.1128/mSystems.00182-17?for a more comprehensive overview of our co-founder Marnix Medema’s research.?