The assembly line of the future: automated tool to help synthetic biology research
A new computer-aided wizard will facilitate the design and synthesis of DNA constructs with speed and efficiency.
Synthetic biology is developing rapidly, with a promising future in various applications, from investigating the behaviour of cancerous cells to minimising carbon footprint. It involves the design and construction of new biological entities such as enzymes and cells, or the redesign of existing biological systems. As such, DNA assembly technologies play a crucial role in advancing synthetic biology. A collaboration between academic and industrial partners supported by the EU-funded TOPCAPI project has recently launched a new DNA assembly tool called the MoCLO wizard.
As stated in a press release published by ‘Bio-IT World’, the new tool “will enable synthetic biologists to rapidly design and synthesise MoCLO CIDAR Level 0 constructs, choosing from hundreds of validated standard biological parts or using custom DNA sequences.” Thanks to the automation of this step, “the time spent by synthetic biologists on DNA design will be reduced and efficiency of their research increased.” The press release also notes that the tool will be particularly relevant to early-career synthetic biologists.
The ongoing TOPCAPI (Thoroughly Optimised Production Chassis for Advanced Pharmaceutical Ingredients) project aims to harness the biosynthetic power of actinomycete bacteria. It will create microbial cell factories for the production of high-value pharmaceuticals, as summarised on the project website. These microorganisms or cell factories are required for the production of most antibiotics that are available today. In fact, actinomycetes are known to produce over 80 % of the natural products that have inspired commercially used antibiotics. Genome sequences show that they collectively provide the largest pool of secondary metabolites. “Thus, actinomycetes are evolutionarily optimised to be producers of natural products, making them potentially the best production host for heterologous high-value compounds.”
TOPCAPI targets two actinomycete hosts that have been studied in great detail since the 1950s: Streptomyces rimosus and Streptomyces coelicolor. The project website explains that “typical industrial strains have been genetically manipulated and are far removed from their ‘wild-type’ ancestors". It adds, however, that “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 these species with industry-level improved performance for the production of bioactive compounds. By developing new bacterial strains for the production of antibiotics, TOPCAPI will help tackle the problem of antimicrobial resistance.
Although antibiotics have had a dramatic impact on the treatment of infectious disease, their misuse or overuse has led to a rise in resistance and the emergence of superbugs. For example, methicillin-resistant Staphylococcus aureus (MRSA) is one of the most frequent causes of antibiotic-resistant healthcare-associated infections worldwide, as highlighted in a report by the European Centre for Disease Prevention and Control. The work of TOPCAPI will also help control the spread of potentially deadly MRSA infections. Another compound developed as part of TOPCAPI will enable the production of a new topical anti-acne drug.