Metabolic engineering of Escherichia coli for the biosynthesis of various phenylpropanoid derivatives

Plants produce a variety of natural products with promising biological activities, such as the phenylpropanoids resveratrol and curcumin. While these molecules are naturally assembled through dedicated plant metabolic pathways, combinatorial biosynthesis has become an attractive tool to generate desired molecules. In this work, we demonstrated that biosynthetic enzymes from different sources can be recombined like legos to make various molecules. Seven biosynthetic genes from plants and bacteria were used to establish a variety of complete biosynthetic pathways in Escherichia coli to make valuable compounds. Different combinations of these biosynthetic bricks were made to design rationally various natural product pathways, yielding four phenylpropanoid acids (cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid), three bioacrive natural siilbenoids (resverairol, picearannol and pinosylvin), and three natural curcuminoicls (curcumin, bisclemerhoxycurcumin and clicinnarnoylmethane). A curcumin analog dicaffeoylmelhanc was synthesized by removing a merhyliransferase from the curcumin biosynthetic pathway. Furthermore, introduction of a fungal flavin-dependera halogenase into the resverairol biosynthetic pathway yielded a novel chlorinated molecule 2-chloro-resverairol. This work thus provides a novel and efficient biosynthetic approach to creating various bioactive molecules. Further expansion of the library of the biosynthetic bricks will provide a resource for rational design of various phenylpropanoids via the combinatorial biosynthesis approach. (C) 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.