P115: Metabolic pathway redesign for specific retinoids production from Escherichia coli

Retinoids are lipophilic isoprenoids molecules, which are defined as a class of chemical compounds that are related chemically to vitamin A. Retinoids include retinol, retinal, retinoic acid, and retinyl esters, and also exist in other various structures differentiated by their functional groups.

The cleavage of β-carotene by BCM(D)O (E.C. 1.13.11.21 or E.C. 1.14.99.36) is the initial key step of synthesis of various retinoids from β-carotene. BCM(D)O cleaves the central double bond (15, 15’) of the polyene chain of β-carotene to yield two molecules of retinal. Retinal is converted to retinol and retinoic acid by retinol dehydrogenase and retinal dehydrogenase/oxidase, respectively. Retinol is esterified to retinyl esters by retinol acyltransferase. The formation of other retinoids derived from retinal by promiscuous enzymes in E. coli was considered. Because retinal could be converted into retinol, retinoic acid, and retinyl ester by cellular enzymatic reactions, these retinal derivatives were analyzed in E. coli culture. Based on this result, the retinoid synthesis pathway of E. coli was reengineered to produce a specific retinoid through elaborative genetic manipulations, such as gene deletions and overexpression of genes involved in the modification of retinoids. Therefore, recombinant E. coli can produce specific retinoids by using retinoids modification enzymes. This work was supported by a grant (NRF-2010-C1AAA001-0029084) from the National Research Foundation, the Intelligent Synthetic Biology Center of Global Frontier Project funded by the MEST (2011-0031964), and a grant from the Next-Generation BioGreen 21 Program (SSAC, grant#:PJ009522003), RDA, Korea.