Enhancing the yield of industrial Actinomycete fermentations
Lead Research Organisation:
University of Strathclyde
Department Name: Inst of Pharmacy and Biomedical Sci
Abstract
A new and radical approach to strain construction is needed for the UK to remain competitive in manufacturing off-patent antibiotics. Antibiotic fermentation processes balance nutrients and cell growth rate with the chemical and physical environments. Cellular output is traditionally improved by selecting higher-producing mutants and optimising fermentation media. However, many antibiotics are unstable in the extracellular environment, with well characterised relationships between pH and degradation rate. The pH range for operation of the biological system often conflicts with the optimum for chemical stability of the product. For an established commercial process we propose to utilise recent advances in synthetic biology and genomics to develop a bacterial strain and industrial fermentation process capable of operating at a lower pH, facilitating stability of the desired product.
Technical Summary
A new and radical approach to strain construction is needed for the UK to remain competitive in manufacturing off-patent antibiotics. Antibiotic fermentation processes balance nutrients and cell growth rate with the chemical and physical environments. Cellular output is traditionally improved by selecting higher-producing mutants and optimising fermentation media. However, many antibiotics are unstable in the extracellular environment, with well characterised relationships between pH and degradation rate. The pH range for operation of the biological system often conflicts with the optimum for chemical stability of the product. For an established commercial process we propose to utilise recent advances in synthetic biology and genomics to develop a bacterial strain and industrial fermentation process capable of operating at a lower pH, facilitating stability of the desired product.
Planned Impact
As described in proposal submitted to IUK
People |
ORCID iD |
Paul Hoskisson (Principal Investigator) | |
Iain Hunter (Co-Investigator) |
Publications
Hoskisson PA
(2018)
Regulation of specialised metabolites in Actinobacteria - expanding the paradigms.
in Environmental microbiology reports
Fernández-MartÃnez LT
(2019)
Expanding, integrating, sensing and responding: the role of primary metabolism in specialised metabolite production.
in Current opinion in microbiology
Schniete J
(2020)
ActDES - a Curated Actinobacterial Database for Evolutionary Studies
Chevrette MG
(2020)
Evolutionary dynamics of natural product biosynthesis in bacteria.
in Natural product reports
Schniete JK
(2021)
ActDES - a curated Actinobacterial Database for Evolutionary Studies.
in Microbial genomics
Feeney M
(2022)
ActinoBase: tools and protocols for researchers working on Streptomyces and other filamentous actinobacteria
in Microbial Genomics