Creation of an Engineered Amide Synthetase Biocatalyst by the Rational Separation of a Two-Step Nitrile Synthetase.

The synthesis of amides through acid and amine coupling is one of the most commonly used reactions in medicinal chemistry, yet still requires atom-inefficient coupling reagents. There is a current demand to develop greener, biocatalytic approaches to amide bond formation. The nitrile synthetase (NS) enzymes are a small family of ATP-dependent enzymes which catalyse the transformation of a carboxylic acid into the corresponding nitrile via an amide intermediate. The Bacillus subtilis QueC (BsQueC) is an NS involved in the synthesis of 7-cyano-7-deazaguanine (CDG) natural products. Through sequence homology and structural analysis of BsQueC we identified three highly conserved residues, which could potentially play important roles in NS substrate binding and catalysis. Rational engineering led to the creation of a NS K163A/R204A biocatalyst that converts the CDG acid into the primary amide, but does not proceed to the nitrile. This study suggests that NSs could be further developed for coupling agent-free, amide-forming biocatalysts.

Improving access to refugee-focused health services for people from refugee-like backgrounds in south-eastern Melbourne through the education sector.

People from refugee-like backgrounds living in Australia face substantial health challenges that benefit from access to health and social services. Many people from refugee-like backgrounds have frequent contact with education sector staff, who have the potential to act as conduits to health and social services. The aim of this project was to improve access to refugee-focused health services for people from refugee-like backgrounds in south-eastern Melbourne by codesigning and delivering a 1-day education forum to education sector staff. Evaluation of the forum used mixed-methods analysis of data from pre-post and follow-up surveys (n=11; administered before, immediately after and 1 month after the forum respectively), post-forum interviews (n=4) and one school's referral records. The forum improved attendees' refugee-focused health service referral knowledge, confidence and behaviour. This was supported by the qualitative findings of high staff motivation, high forum satisfaction and evidence of outcome sustainability. Education staff are an important complement to an integrated model of health care for recently resettled people from refugee-like backgrounds. These results show that a straightforward local intervention can improve the ability of education staff to act as conduits to health services, increasing access to health services for people from refugee-like backgrounds.