PhD project title and outline, including interdisciplinary dimension:
Enzyme Discovery from the Salt of the Earth: Discovery of transaminase enzymes from extremely halophilic microorganisms from an ancient hypersaline environment for Active Pharmaceutical Ingredient (API) synthesis

The overall aim of this research project is to discover novel transaminase biocatalysts from extremely halophilic archaea both from cultured isolates and metagenomic data sets from Triassic halite evaporites (Kilroot salt mine, Carrickfergus), for application in production of active pharmaceutical ingredients (APIs) and fine chemical synthesis. Our group has already been successful in developing a large bank of bacterial and archaeal isolates and metagenomic data sets from this unique environments (the only group to have done so), and have been successful in developing a robust platform for molecular cloning and expression of both bacterial and archaeal proteins. The microbiome of this unique environment (both culturable and non-culturable) represents an exciting, untapped, potential resource for novel biocatalysts for active pharmaceutical ingredient (API) synthesis. In combining complementary expertise of the academic and industry applicants, we aim to exploit the potential of extreme halophiles from ancient halite deposits for the development of novel, optimized API biocatalytic platforms. Specifically, research will focus on the high-throughput screening and isolation of transaminases from extreme halophilic species and their optimization through directed evolution approaches. Thus, the proposal will develop a novel screening platform and a panel of native and optimized transaminases (from both culturable and unculturable microorganisms) for a broad range of applications.

Almac Sciences has established a strong, energetic biocatalysis group with a dedicated building for research with state-of-the-art facilities. This group has been successful in producing multiple enzyme screening kits, bulk enzyme supply and enzyme development projects. In the process Almac have published a number of posters and papers and have promoted the business with new and existing customers. Their capability is currently limited by the range of novel enzymes and enhanced bio-oxidative enzymes that Almac can offer is the subject of this application.

The PhD programme will have a clear academic-industry interface with the delivery of enzymes that have direct commercial opportunities and an industrial relevantly trained PhD graduate. The key opportunities to the student will encompass: the chance to work at the highly productive interface between academic research and industrial application.  The student will be working in a high technology field and will be conversant in the day-to-day research of the industrial partner; together with the potential to learn the latest developments in bioprocess and associated research methods from a leading academic group with over 15 years related experience and an international publications record in the field. With these opportunities will come a challenge to actually implement recent academic developments in the field to develop and implement bioprocesses that are highly relevant to the interest of the partner company; this will require experience to be gained in working at the interface of 3 technical disciplines – organic chemistry; molecular biology/microbiology/biosciences and process engineering.  The candidate will also learn programming languages and bioinformatics. These requirements will also afford a unique and highly challenging opportunity and learning experience/training to the student. Both the academic and industry partners have a wide range of international collaborators and visits to collaborators’ laboratories will form an integral part of the training programme (in addition to presentation of outcomes at relevant, leading international conferences).

Primary Supervisor: Professor Brendan Gilmore (Pharmacy)
Secondary Supervisor: Dr Timofey Skvortsov (Pharmacy)
External Partner/Organisation: Almac and Arran Chemicals