PECASE: Bioengineering of Secondary Metabolic Pathways

University Of California-Los Angeles, Los Angeles CA

Investigators

Abstract

Tang 0545860 Tetracyclines have been prescribed as broad-spectrum antibiotics and have recently been used in anticancer therapies. The objective of this research is to understand the metabolic pathway, the molecular assembly, and the combinatorial potential of tetracycline biosynthesis. Four specific aims will be pursued: (1) Reconstitute and understand the assembly of the amidated tetracycline backbone; (2) Reconstitute the first tetracyclic intermediate in oxytetracycline (oxy) pathway and use metabolic engineering to produce a novel C8-hydroxylated analog of the intermediate; (3) Reconstitute the tailoring steps in oxy pathway and construct a series of strains that can produce valuable metabolic intermediates; (4) Engineered biosynthesis of novel glycosylated analogs of tetracycline through shuffling of heterologous secondary metabolic pathways. The research and education efforts will be integrated through the following mechanisms: 1) Two recently developed, core biotechnology courses will be enriched to increase critical thinking and active learning by the students; 2) Community outreach will be emphasized by inviting underprivileged minority students in the greater Los Angeles metropolitan area to learn research during the summer months, as well as participating in university-community events to promote science education and life-long learning.