SYNTHESIS OF LONG CHAIN DICARBOXYLIC ACIDS IN CELL FACTORIES USING SYSTEMS AND SYNTHETIC BIOTECHNOLOGY APPROACH

Abstract

Aliphatic dicarboxylic acids (DCAs) produced from microorganisms can be a sustainable alternative to petroleum-derived processes. The primary objective of this work was to assess and exploit the systems and synthetic biotechnology approaches to improve microorganisms for their ability to convert carbon substrates into DCAs. Initially, we aimed to extend existing systems biology tools for understanding the metabolic behavior of Candida tropicalis, capable of producing DCAs. Next, C. tropicalis was utilized as microbial chassis for whole cell biotransformation to produce Dodecanedioic acid (DDDA). Further, we studied Yarrowia lipolytica to design strain development approach to examine metabolic targets for DDDA overproduction. In parallel, we engineered E. coli to overproduce DCAs using reversal of β-oxidation cycle. Through the amalgamation of GSMM analysis and engineering E. coli to overproduce DCA, this thesis undertook to build an understanding of conventional and non-conventional microbial cell factories to aid the rational engineering of an efficient microbial system.