Assembly of Dynamic P450-Mediated Metabolons-Order Versus Chaos

Abstract

Purpose of review: We provide an overview of the current knowledge on cytochrome P450-mediated metabolism organized as metabolons and factors that facilitate their stabilization. Essential parameters will be discussed including those that are commonly disregarded using the dhurrin metabolon from Sorghum bicolor as a case study.

Recent findings: Sessile plants control their metabolism to prioritize their resources between growth and development, or defense. This requires fine-tuned complex dynamic regulation of the metabolic networks involved. Within the recent years, numerous studies point to the formation of dynamic metabolons playing a major role in controlling the metabolic fluxes within such networks.

Summary: We propose that P450s and their partners interact and associate dynamically with POR, which acts as a charging station possibly in concert with Cytb5. Solvent environment, lipid composition, and non-catalytic proteins guide metabolon formation and thereby activity, which have important implications for synthetic biology approaches aiming to produce high-value specialized metabolites in heterologous hosts.

Keywords: Channeling; Cytochrome P450 oxidoreductase; Cytochromes P450; Membrane environment; Metabolon; Solvent environment.

Fig. 1

Pubmed occurrences about metabolon papers. Pubmed (https://www.ncbi.nlm.nih.gov/pubmed) queried towards the end of November 2016. With the queries: “protein-protein interaction,” “protein complex,” metabolon, and plant and metabolon

Fig. 2

Representation of a protein array at the ER surface. ER-anchored protein molecules are each represented by a white dot. A total of 4960 protein molecules are displayed

Fig. 3

Models 1, 2, and 3. a Model 1 of a random distribution of dynamic proteins. All the proteins are freely moving and only interact by random “hit-and-run” mechanism. b Model 2 of stable metabolons. This model involves pre-formed metabolons that are exchanged to the POR acting as a charging station. c Models 3a, b and c of proteins organized in large structures. Model 3a, proteins organized in highways across the ER tubule with POR trapped inside the highways. Model 3b, proteins organized in highways across the ER tubule with POR freely moving around the highways. Model 3c, proteins organized in aggregates with freely moving POR

Fig. 4

Models 4 and 5 of proteins organized as dynamic metabolons. a Model 4a, mixed metabolons are formed around the POR acting as a charging dock. Model 4b, POR encircled by one or mixed metabolons. b Model 5 of formation of specific transient and dynamic metabolon around the POR. Only one metabolon is present at a time t around the POR. This model implies a dynamic exchange of metabolon components around a POR acting as a charging station. Metabolons could be formed by oligomers of each component. Association and dissociation of metabolons are controlled upon cellular needs. Three arbitrary time points are shown in this figure