Improvement
Increasing biomass, metabolic output and efficiencies in scale-up
Strain engineering of Actinobacteria to unlock their full potential
Project: A platform for functional prediction and validation of undiscovered secondary metabolites in Actinobacteria (2023-2027). Part of the Advanced Engineering Biology Future Science Platform
Project: Biocontrol strain improvement, funded by the CSIRO Research Office.
The team: Marta Gallart (Project leader), Louise Thatcher (Project leader), Oliver Mead, Vincent Nowak, Lygie Esquirol, Margaret Ramarajan, Rosangela Devilla, Alan Richardson.
The challenge
Actinobacteria are a rich source of natural products with a variety of bioactivities. Traditionally strains are cultivated in the laboratory, a chemical extraction is performed and compounds of interest identified. However, even with the use of different cultivation media some compounds are not produced. Genetic engineering of strains has emerged as a promising approach to elicit production of some of these compounds. While the Streptomyces genus has been studied rigorously and several approaches for genetically engineering this genus exist, some other genera of Actinobacteria have not been adequately studied. These lesser studied genera not only hold promise for new bioactive molecules but also require further characterisation and method development for genetic engineering.
Our response
High-throughput engineering of our in-house strain collection of mostly endophytic Actinobacteria will identify genetically tractable strains and allow further characterisation of their chemical potential and bioactivities. In addition, targeted engineering of Streptomyces strains will also be carried out to attempt elicitation of biosynthetic pathways of interest. Building on these results, we will attempt to develop protocols for non-tractable strains and work on domesticating these strains for genetic engineering experiments. We also apply non-GM approaches for domestication; utilizing high throughput bioassays or reporter systems to monitor outputs from mutagensised bacterial populations.
Impact
Biocontrol agents offer a safer, sustainable and more effective solution to maintain high productivity agricultural systems. This project is largely focused on herbicidal bioactivity but within the team we have capability to test for antifungal and insecticidal activity, plus other teams at CSIRO can test for other bioactivities. Using the engineered strains in combination with bioassays for herbicidal activity will determine if any of the strains in the collection could be used for weed control in an agricultural setting.
Learn more here
El-Hawary, S. S., Hassan, M. H., Hudhud, A. O., Abdelmohsen, U. R., & Mohammed, R. (2023). Elicitation for activation of the actinomycete genome’s cryptic secondary metabolite gene clusters. RSC advances, 13(9), 5778-5795. https://doi.org/10.1039/D2RA08222E