Synthetic biology strategies toward heterologous phytochemical production

Abstract

Covering: 2006 to 2018 Phytochemicals are important sources for the discovery and development of agricultural and pharmaceutical compounds, such as pesticides and medicines. However, these compounds are typically present in low abundance in nature, and the biosynthetic pathways for most phytochemicals are not fully elucidated. Heterologous production of phytochemicals in plant, bacterial, and yeast hosts has been pursued as a potential approach to address sourcing issues associated with many valuable phytochemicals, and more recently has been utilized as a tool to aid in the elucidation of plant biosynthetic pathways. Due to the structural complexity of certain phytochemicals and the associated biosynthetic pathways, reconstitution of plant pathways in heterologous hosts can encounter numerous challenges. Synthetic biology approaches have been developed to address these challenges in areas such as precise control over heterologous gene expression, improving functional expression of heterologous enzymes, and modifying central metabolism to increase the supply of precursor compounds into the pathway. These strategies have been applied to advance plant pathway reconstitution and phytochemical production in a wide variety of heterologous hosts. Here, we review synthetic biology strategies that have been recently applied to advance complex phytochemical production in heterologous hosts.

Integrating pathway elucidation with yeast engineering to produce polpunonic acid the precursor of the anti-obesity agent celastrol

“…In the case of celastrol, this approach will enable its efficient stereo-specific biosynthesis and the production of derivatives in adequate amounts. The model organism Saccharomyces cerevisiae (baker's yeast) is an established host for the efficient production of industrial chemicals and complex highvalue compounds [23][24][25]. This is due to its amenability to genetic engineering, relative absence of secondary metabolites, and its compatibility with most key eukaryotic biosynthetic enzymes, such as cytochromes P450 (P450s), enabling the reconstruction of complete biosynthetic pathways.…”

Characterizing standard genetic parts and establishing common principles for engineering legume and cereal roots

“…Plant synthetic biology seeks to engineer novel traits into plants, and these engineering efforts need to be specifically directed in crop species to be of agronomic relevance (Kotopka et al, 2018;Liu and Stewart, 2015). The engineering of cereals in particular offers up a unique set of challenges, especially as many of the existing tools for plant synthetic biology have been developed for model dicotyledonous plant species.…”

Native and non-native host assessment towards metabolic pathway reconstructions of plant natural products

“…Microbial bioreactor systems are inevitable for the commercial production of many essential compounds. Engineering Escherichia coli and Saccharomyces cerevisiae demand biosynthetic pathway regulation [ 34 ]. For the production of Naringenin and p-Coumaric acid (necessary intermediates of flavonoid biosynthetic pathway), the flavonoid pathway is refactored in E. coli and S. cerevisiae [ 35 ].…”