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Bacteriocins are unique biological products produced by a vast range of bacteria able to target and kill specific microbial strains or species. These qualities give bacteriocins great potential for many different industries, including human and animal health, the production and storage of food and animal feeds, and industrial fermentation. In fact, bacteriocins have a potential role in any industry that uses fermentation or in which microbes play.
Current bacteriocin databases classify bacteriocins based on their structural features such as extensive post-translational modification or bacteriocins that are active as two-component systems.
To take advantage of the wide range of potential applications, we are building an in-house collection, Syngulon’s PARAGEN collection, based on a bacteriocin DNA library. In addition to “natural” bacteriocins, we will use synthetic biology to tune and create de novo peptides based on the needs of our industrial partners. These can be used in combination (“cocktails”) to finely adjust microbial community composition. Classification of these natural and synthetic bacteriocins and their many combinations can be made based on their industrial application. Indeed, our experimental data show the potential for bacteriocins to work in combination.
Examples of bacteriocin design:
Bacteriocin qualities can be changed through simple modifications, from minor changes to the amino acid sequence to the removal or addition of secondary modifications. These changes can affect the level of bacteriocin activity as well as species or strain target specificity. For examples, the bacteriocin Enterocin AS-48 is a circular peptide with a C-terminal tryptophan joined to an N-terminal methionine in the mature peptide. Circularization occurs through the activity of several accessory genes in the bacteriocin genetic locus. However, activity of this bacteriocin can still be observed when it is produced as a linear peptide; this can be done by mutating the C-terminal tryptophan to an alanine residue unable to bind to the N-terminal methionine, or through expression of the bacteriocin gene (Sanchez-Hidalgo et al. 2011).
Additionally, bacteriocin hybrids have been demonstrated to enhance the target spectrum. Swapping the N-termini of Pediocin PA-1 and Enterocin 50-52 demonstrated that a hybrid bacteriocin capable of killing both Gram-positive and Gram-negative targets even when one of the wild-type bacteriocins has no activity against Gram-negative bacteria (Tiwari et al. 2015).
We currently use bacteriocins as selective agents in microbial fermentation. We envision expanding the use of bacteriocins to reshape the microbial community as needed. To this end, bacteriocins can be used not only individually, but in “cocktails” containing multiple bacteriocins, each one targeting a specific microbial strain or species. The desired result can be either the elimination of unwanted strains, or the maintenance of a certain proportion of strains.
To facilitate this “microbial community engineering”, we are building a collection of bacteriocins that we can deploy against any possible contaminant, or for shaping a microbial community as needed. The current academic classification system separates bacteriocins into lantibiotics and non-lantibiotics, and further subdivides this second group based on similarity to pediocins (a certain type of bacteriocin), two-component systems, circular bacteriocins, and larger, protein-like bacteriocins. This system is updated and restructured as novel bacteriocins and bacteriocins with differing characteristics are discovered.
We wish to build a classification system for our PARAGEN collection based on the needs of our industrial partners. This could include bacteriocins specific for certain species, or bacteriocins that work well at certain temperatures or pH levels. It would also include the functionality of certain bacteriocin combinations, as some may complement each other better than others. This will be determined by data collected at bench and industrial scales, as well as through systems modelling of bacteriocin and microbe interaction.
Finally, we will add to this PARAGEN collection bacteriocins created or adapted through synthetic biology. In all, this will provide a powerful toolbox to shape microbial communities based on the needs of our customers.