Microbial production of natural and non-natural flavonoids: Pathway engineering, directed evolution and systems/synthetic biology

Abstract

In this review, we address recent advances made in pathway engineering, directed evolution, and systems/synthetic biology approaches employed in the production and modification of flavonoids from microbial cells. The review is divided into two major parts. In the first, various metabolic engineering and system/synthetic biology approaches used for production of flavonoids and derivatives are discussed broadly. All the manipulations/engineering accomplished on the microorganisms since 2000 are described in detail along with the biosynthetic pathway enzymes, their sources, structures of the compounds, and yield of each product. In the second part of the review, post-modifications of flavonoids by four major reactions, namely glycosylations, methylations, hydroxylations and prenylations using recombinant strains are described.

Metabolic Engineering of Microorganisms for the Production of Natural Compounds

“…[111] The stilbene synthase is related to the chalcone synthase but its mechanism of action is distinct. Further modifications are carried out by cytochrome P450 hydroxylases, NADPH-dependent reductases, 2-oxoglutaratedependent dioxygenases, O-methyltransferases, acyltransferases, and glycosyltransferases.…”

“…In this situation, microbial production can be a great alternative for the phenylpropanoids production. [111] To this end, many researchers worldwide have been aiming at constructing the microbial cell factories for high-level production of these chemicals.…”

Stepwise modular pathway engineering of Escherichia coli for efficient one-step production of (2S)-pinocembrin

“…Microbial bioconversion and fermentation are expected to revolutionize the conventional extraction of flavonoids from plant natural resources (Pandey et al, 2016;Xu et al, 2013;Zhou et al, 2014). However, broad adoption of microbial synthesis is hampered because it is a costly and inefficient process, typically requiring the supplementation of expensive precursors in the media and two separate fermentation steps (Santos et al, 2011).…”

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

“…It is therefore essential to develop a greater knowledge of the decorating enzymes specific to berry bioactives, such as those differentially decorating anthocyanins, flavonols, stilbenes, or condensed tannins. Many genes encoding enzymes involved in flavonol and anthocyanin decoration have already been characterized not only in planta, but also heterologously in microorganisms, such as Escherichia coli and S. cerevisiae (Tohge et al 2005;Luo et al 2007;Pandey et al 2016;Wang et al 2016a).…”

“…Moreover, it is one of the best studied organisms, easy to handle, and a much larger set of genetic tools is available for this organism compared to other bacteria (Yu et al 2011;Dobson et al 2012;Chen et al 2013). Furthermore, E. coli has been previously used for heterologous production of polyphenolic compounds (Pandey et al 2016;Wang et al 2016a). …”