Exploring the role of MtrD and WblA in regulating development and antibiotic biosynthesis in Streptomyces

Tulley, Kelly-Rose (2025) Exploring the role of MtrD and WblA in regulating development and antibiotic biosynthesis in Streptomyces. Doctoral thesis, University of East Anglia.

PDF Restricted to Repository staff only until 31 August 2028. Request a copy

Abstract

The ongoing global crisis of antimicrobial resistance (AMR) is escalating, creating an urgent demand for novel antimicrobial agents. Historically, the Streptomyces genus has provided a plethora of such compounds; however, very few of its encoded biosynthetic gene clusters (BGCs) are expressed under standard laboratory conditions. One way to encourage the expression of these cryptic BGCs is to manipulate the signalling systems of Streptomyces species, including Two-Component Systems (TCSs), like MtrAB. In Streptomyces venezuelae NRRL B-65442, the MtrA response regulator binds to 85% of BGCs, making it a promising candidate for activating cryptic pathways. MtrA also binds upstream of hundreds of other genes, leading to questions over how it achieves specificity. Previous research suggested it interacts with another regulator, named MtrD in this thesis.

This project characterises the MtrD protein and identifies MtrD as an activator of wblA, which encodes a WhiB-like (Wbl) family protein that has pleiotropic effects on specialised metabolism and life cycle development in Streptomyces species. Additionally, this thesis defines the WblA regulon for the first time, offering new insights into its regulatory function. Finally, this project briefly discusses the possibility of MtrA-MtrD heterodimerisation.

By clarifying the roles of MtrD and WblA, this research enhances our understanding of Streptomyces biology. Increased knowledge of Streptomyces regulatory pathways will enable researchers to tap into the incredible biosynthetic potential of these bacteria through regulatory engineering to address AMR.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Kitty Laine
Date Deposited:	06 May 2026 13:04
Last Modified:	06 May 2026 13:04
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102916
DOI:

Actions (login required)

View Item