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Boris Zacchetti - Tinkering with bacterial production

Biotechnologist Boris Zacchetti enhanced the performances of Streptomyces bacteria, which are used to produce antibiotics and valuable enzymes. He discovered that certain genes are responsible for the formation of particles with highly different sizes, which has a negative impact on production performances. ‘My discoveries could contribute to the availability of cheaper or novel products for consumers.’

Antibiotics production

Zacchetti focused on the filamentous bacteria Streptomyces. These bacteria form long strands growing end to end, resembling strands of hair or spaghetti, which interlock to form a mesh. The industrial biotechnology sector grows liquid cultures of streptomycetes to obtain a variety of commercially valuable products, such as antibiotics and hydrolytic enzymes, which are efficient biological catalysts. However, these bacteria often perform poorly in this kind of cultures. ‘One of the biggest problems is the fact that streptomycetes form particles with highly different sizes’, Zacchetti explains. 'This phenomenon bears a negative impact on their production performances.’ Zacchetti now discovered which process and underlying genes are responsible for this heterogeneity.

Aggregation

In contrast to most other bacteria, streptomycetes grow by forming thread-like cells. These threads then grow and branch to form complex networks of interconnected cells, called mycelia. The morphology of these networks, and the heterogeneity of the cells, highly influence their final productivity. Zacchetti discovered that certain glycans (or polysaccharides) on the outside of the cells play a vital role in shaping mycelia. Furthermore, glycans also turned out to mediate aggregation between different mycelia. This process of aggregation generates larger mycelial structures composed of different individuals, in other words: a heterogeneous population.

It’s in the genes

Zacchetti found that three genes are responsible for this aggregation. The absence of these genes results in a lack of glycan formation, which prevents different structures from being glued together. This yields mycelia that originate from individual cells and that all have the same size, which leads to a homogeneously distributed population. By gaining control over this process, Zacchetti was able to enhance the production performances of streptomycetes.

Rational research

The biology of streptomycetes in submerged cultures is still poorly understood. The optimisation of the existing production processes heavily relies on trial and error procedures. In such methods, the mechanisms underlying enhanced performances are often overlooked. Zacchetti states that his research will greatly contribute to the optimization of streptomycetes in a more rational matter, as opposed to previous blind approaches. He furthermore emphasises the fact that production strains that are more amenable under industrial settings translate into lower prices for the overall process and the final products in turn. ‘In this context, my discoveries could contribute to cheaper or novel products, such as antibiotics, becoming available to consumers with all the advantages that would entail.'

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