A retrosynthetic biology approach to metabolic pathway design for therapeutic production

摘要: Synthetic biology is used to develop cell factories for production of chemicals by constructively importing heterologous pathways into industrial microorganisms. In this work we present a retrosynthetic approach the therapeutics with goal developing an in situ drug delivery device host cells. Retrosynthesis, concept originally proposed synthetic chemistry, iteratively applies reversed chemical transformations (reversed enzyme-catalyzed reactions metabolic space) starting from target product reach precursors that are endogenous chassis. So far, wider adoption retrosynthesis manufacturing pipeline has been hindered complexity enumerating all feasible biosynthetic given compound. our method, efficiently address problem coding substrates, products and molecular signatures. Metabolic maps represented using hypergraphs controlled varying specificity signature. Furthermore, method enables candidate be ranked determine which ones best engineer. The ranking function can integrate data different sources such as compatibility inserted genes, estimation steady-state fluxes genome-wide reconstruction organism's metabolism, or metabolite toxicity experimental assays. We use several machine-learning tools order estimate enzyme activity reaction efficiency at each step identified pathways. Examples bacteria yeast two antibiotics one antitumor agent, well essential metabolites outlined. here unified framework integrates diverse techniques involved design through signature space. Our engineering methodology flexible microorganisms efficient on-demand compounds therapeutic applications.