报告人: Prof. Eriko Takano Chemical Biology and Biological Chemistry
Department of Chemistry Manchester Institute of Biotechnology
Prof. Eriko Takano’s group aim to design and construct organisms with new functionalities of unprecedented scope, by exploiting synthetic biology for metabolic engineering, harnessing our ability to readily sequence complete genomes and to rewrite/re-design pathways on a large scale. They explore these possibilities in the context of chemical production, focusing on antimicrobials as well as flavours and fragrances, utilising the Design/Build/Test/Learn cycle at the Parts, Devices and Systems level. Many microorganisms already have the machinery to produce diverse bioactive molecules that can be used in the health, agriculture and food industries. As a first step towards re-engineering these chemical biosynthesis pathways for enhanced productivity and diversity, they aim to understand the interchangeability of biosynthetic parts and created a minimal information database for natural products with the support from the natural products community. They have designed and assembled pathways using the identified parts and will engineer orthogonal transcription mechanisms based on signalling molecule circuits. In addition, they are expanding their collection of computational tools for the detection and analysis of secondary metabolite biosynthesis gene clusters, to enrich their library of parts and building blocks for pathway engineering. They also use computational modelling to identify suitable overproduction hosts and pinpoint biosynthetic bottlenecks to target for further cellular engineering in a synthetic biology strategy. They combine this analysis with high-resolution mass spectrometry analysis, which they also employ for the debugging of the engineered systems. This finally leads to the completion of the cycle by learning rules for efficient design. By exploiting all these tools in the Design/Build/Test/Learn cycle, the BBSRC/EPSRC-funded Manchester Synthetic Biology Research Centre, SYNBIOCHEM, provides a platform for the high-throughput engineering of fine and speciality chemicals production in microbial systems.