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

Abstract

Plant-based biopreparations are reasonably priced and are devoid of viral, prion and endotoxin contaminants. However, synthesizing these natural plant products by chemical methods is quite expensive. The structural complexity of plant-derived natural products poses a challenge for chemical synthesis at a commercial scale. Failure of commercial-scale synthesis is the chief reason why metabolic reconstructions in heterologous hosts are inevitable. This review discusses plant metabolite pathway reconstructions experimented in various heterologous hosts, and the inherent challenges involved. Plants as native hosts possess enhanced post-translational modification ability, along with rigorous gene edits, unlike microbes. To achieve a high yield of metabolites in plants, increased cell division rate is one of the requisites. This improved cell division rate will promote cellular homogeneity. Incorporation and maintenance of plant cell synchrony, in turn, can program stable product scale-up.

Keywords: HEx, heterologous expression; Heterologous hosts; Metabolic engineering; PTM, post-translational modification; Single plant cells; Synthetic biology; TEAMP, Transient Expression in Arabidopsis Mesophyll Protoplast; TOR, Target of Rapamycin; Transgenesis.

Fig. 1

Metabolic refactoring in heterologous hosts a. Identification of biosynthetic gene clusters b. Consideration of the metabolic network and flux regulations in native hosts and non-native hosts using a synthetic biology approach c. Determination of the gene responsible for the compound of interest and causes for flux perturbations and upgrading the metabolic network using gene editing and promoter engineering followed by pathway refactoring in suitable heterologous hosts d. Post refactoring analysis in non-native hosts along with precursor input and metabolite output evaluations.