Background

TOPCAPI is a collaboration between academic and industrial experts that will harness the power of actinomycete bacteria to create microbial cell factories for the production of high-value pharmaceuticals, in particular antibiotics.

Antibiotics are compounds produced naturally by microorganisms that inhibit or kill, other microorganisms.  Penicillin, likely to be the best known antibiotic, is produced by the fungus Penicillium chrysogenum and was the first antibiotic to be produced on an industrial scale.

Antibiotics have had a dramatic impact on the treatment of infectious disease; unfortunately, overuse or, misuse, of antibiotics has led to a rise in resistance and the emergence of multi-drug resistant ‘superbugs’. As a result, although there are over 100 antibiotics commercially available, bacterial infections still represent an area of acute unmet medical need and may yet again become a more deadly threat to mankind than cancer, if we don’t act now. Against this backdrop of increasing need, the British Society for Antimicrobial Chemotherapy Initiative noted in 2011 that ‘the [antibiotic] pipeline is at its lowest ebb since the early 1940s when penicillin was developed (1).

The aim of the TOPCAPI project is to develop new bacterial strains for the production of antibiotics, to help tackle the problem of antimicrobial resistance.


What will TOPCAPI do?

Most antibiotics available today require a microorganism, or “cell factory”, to produce them. That organism must be capable of growing rapidly in large-scale culture and of producing the desired product in a short period of time. Typical industrial strains have been genetically manipulated and are far removed from their “wild-type” ancestors.   Streptomycetes are one group of organisms used for the production of antibiotics, and there are two species of particular interest to the TOPCAPI project: Streptomyces rimosus and Streptomyces coelicolor. These soil-dwelling bacteria have been studied in great detail since the 1950s, and their most striking property is the extent to which they produce antibiotics. Specifically, 35% of all antibiotics sold today contain an active ingredient derived from a Streptomyces species, or one of its close relatives (2). However, there is no single, robust Streptomyces cell factory available for the high level production of different compounds in an industrial context, and most of the compounds produced can only be obtained at sufficient levels after exposing the host organism to several rounds of labour-intensive genetic manipulation and screening for enhanced metabolite production.

TOPCAPI aims to engineer two Streptomyces species to produce industry-level improved performance for the production of bioactive compounds.


References:

1: The Urgent Need, Regenerating antibacterial drug discovery development. Report of the British Society for Antimicrobial Chemotherapy Initiative

2: Gomez-Escribano J. P and Bibb M. J. J Ind Microbiol Biotechnol. (2014) 41: 425-31).


This project has received funding from the European Union’s Horizon 2020 Research and Innovation programme under Grant Agreement No. 720793