The challenges of cellular compartmentalization in plant metabolic engineering

The complex metabolic networks in plants are highly compartmentalized and biochemical steps of a single pathway can take place in multiple subcellular locations. Our knowledge regarding reactions and precursor compounds in the various cellular compartments has increased in recent years due to innovations in tracking the spatial distribution of proteins and metabolites. Nevertheless, to date only few studies have integrated subcellular localization criteria in metabolic engineering attempts. Here, we highlight the crucial factors for subcellular-localization-based strategies in plant metabolic engineering including substrate availability, enzyme targeting, the role of transporters, and multigene transfer approaches. The availability of compartmentalized metabolic network models for plants in the near future will greatly advance the integration of localization constraints in metabolic engineering experiments and aid in predicting their outcomes.

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► Targeting enzymes to organelles with highest precursor pool affects product yield.
► Targeting of nonendogenous enzymes to organelles is a useful tool for engineering.
► Identification of transporters is central for effective metabolic engineering.
► Advances in metabolomics of isolated organelles will impact engineering strategies.
► Future plant metabolic engineering will include introduction of entire pathways.