Research Progress in Area 4 方向 ( 四 ) 課題進展 177 Abstract The field of marine natural products biosynthesis has matured over the last decade to begin solving many of the scientific challenges that limited the biological evaluation of rare marine chemicals due to sample limitations and recollection problems. Prof. Moore’s team aims to strategically biosynthesize two potent families of marine cyclic lipopeptides. First, they will heterologously produce, chemically characterize, and biologically evaluate native and engineered thalassospiramide analogues against a broad panel of biological targets, including the calpain protease. Second, they will apply their gene engineering and broad host expression technology to heterologously produce the didemnin anticancer agents that have long resisted synthetic biology methodologies. Lastly, they will additionally assist team members in the Qian laboratory who study genome mining and heterologous biosynthesis. Research Activities and Progress Delayed the work on the bacterial production of the thalassospiramide calpain protease inhibitors due to the covid-19 pandemic. • Assembled most of the didemnin biosynthesis geneswith synthetic promoters and terminators as separate gene constructs based on a new Loop assembly synthetic biology platform. • Developed a library of synthetic promoters and terminators designed specifically for Pseudomonas host expression that they call pLoop. Key Findings • A novel synbiol technology called Loop Assembly was applied to build the didemnin cluster up from its individual component parts. • It is anticipated that Loop assembly will be useful to other programs in the HKB program who have interest in the expression and production of microbial products. Research Output Publication 0 Trained personnel 0 Biosynthetic Production and Biological Evaluation of Bioactive Marine Natural Products Prof. Bradley Moore University of California San Diego Fig 1. Chemical structure of several natural products.
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