Mobile Genetic Elements as Tools for Engineering Cell Factories
Abstract
This project aims to create a universal platform for engineering a diverse group of microbial cell factories. The platform comprises a collection of tools, based on mobile genetic elements (MGEs), for delivering, maintaining and controlling expression of gene cassette(s) in heterologous microbial hosts. While MGEs such as conjugative plasmids, phages, integrative conjugative elements and transposons have long been used for genetic engineering, I will upgrade their host-range and efficiency by tackling the three critical phases of MGE development- discovery, domestication and design. The discovery phase will focus on systematic database-literature mining for families of broad-host-range MGEs. Lead MGE candidates will be selected based on their host ranges and ability to complement one another’s host ranges. Experimental validation will further eliminate non-functional or inefficient candidates. The domestication phase will focus on refactoring selected MGEs to miniaturize their size and modularize their genetic components. Modularity will allow us to mix-and match components from different MGEs. I will analyse chimeric MGEs to identify key components for host-range and efficiency in delivery, maintenance and expression control. The design phase will improve natural or chimeric MGEs by directed evolution of their genetic components. Selection and screening process will challenge our engineered MGEs in increasingly broader host ranges. MGEs performance across different hosts will be used for building statistical and mechanistic models to guide their usages and improvement. This project will output high performance MGE toolkits and predictive models for at least four commonly used industrial microbes and four undomesticated microbes. The knowhow from this project could help generalize workflows for engineering cell factories as well as deepening our understanding of MGE biology.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Feb 16, 2024
- Source ID
- FA23862314017
Entities
People
- Pakpoom Subsoontorn
Organizations
- Air Force Office of Scientific Research
- Faculty of Medical Science, Naresuan University
- United States Air Force