Metabolons, enzyme–enzyme assemblies that mediate substrate channeling, and their roles in plant metabolism

Metabolons are transient multi-protein complexes of sequential enzymes that mediate substrate channeling. They differ from multi-enzyme complexes in that they are dynamic, rather than permanent, and as such have considerably lower dissociation constants. Despite the fact that a huge number of metabo...

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Main Authors: Youjun Zhang, Alisdair R. Fernie
Format: Article
Language:English
Published: Elsevier 2021-01-01
Series:Plant Communications
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2590346220301048
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author Youjun Zhang
Alisdair R. Fernie
author_facet Youjun Zhang
Alisdair R. Fernie
author_sort Youjun Zhang
collection DOAJ
description Metabolons are transient multi-protein complexes of sequential enzymes that mediate substrate channeling. They differ from multi-enzyme complexes in that they are dynamic, rather than permanent, and as such have considerably lower dissociation constants. Despite the fact that a huge number of metabolons have been suggested to exist in plants, most of these claims are erroneous as only a handful of these have been proven to channel metabolites. We believe that physical protein–protein interactions between consecutive enzymes of a pathway should rather be called enzyme–enzyme assemblies. In this review, we describe how metabolons are generally assembled by transient interactions and held together by both structural elements and non-covalent interactions. Experimental evidence for their existence comes from protein–protein interaction studies, which indicate that the enzymes physically interact, and direct substrate channeling measurements, which indicate that they functionally interact. Unfortunately, advances in cell biology and proteomics have far outstripped those in classical enzymology and flux measurements, rendering most reports reliant purely on interactome studies. Recent developments in co-fractionation mass spectrometry will likely further exacerbate this bias. Given this, only dynamic enzyme–enzyme assemblies in which both physical and functional interactions have been demonstrated should be termed metabolons. We discuss the level of evidence for the manifold plant pathways that have been postulated to contain metabolons and then list examples in both primary and secondary metabolism for which strong evidence has been provided to support these claims. In doing so, we pay particular attention to experimental and mathematical approaches to study metabolons as well as complexities that arise in attempting to follow them. Finally, we discuss perspectives for improving our understanding of these fascinating but enigmatic interactions.
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spelling doaj.art-793a51068419472d8585b98cc175bc2e2022-12-21T19:03:33ZengElsevierPlant Communications2590-34622021-01-0121100081Metabolons, enzyme–enzyme assemblies that mediate substrate channeling, and their roles in plant metabolismYoujun Zhang0Alisdair R. Fernie1Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria; Max-Planck-Institut für Molekulare Pflanzenphysiologie, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany; Corresponding authorCenter of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria; Max-Planck-Institut für Molekulare Pflanzenphysiologie, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany; Corresponding authorMetabolons are transient multi-protein complexes of sequential enzymes that mediate substrate channeling. They differ from multi-enzyme complexes in that they are dynamic, rather than permanent, and as such have considerably lower dissociation constants. Despite the fact that a huge number of metabolons have been suggested to exist in plants, most of these claims are erroneous as only a handful of these have been proven to channel metabolites. We believe that physical protein–protein interactions between consecutive enzymes of a pathway should rather be called enzyme–enzyme assemblies. In this review, we describe how metabolons are generally assembled by transient interactions and held together by both structural elements and non-covalent interactions. Experimental evidence for their existence comes from protein–protein interaction studies, which indicate that the enzymes physically interact, and direct substrate channeling measurements, which indicate that they functionally interact. Unfortunately, advances in cell biology and proteomics have far outstripped those in classical enzymology and flux measurements, rendering most reports reliant purely on interactome studies. Recent developments in co-fractionation mass spectrometry will likely further exacerbate this bias. Given this, only dynamic enzyme–enzyme assemblies in which both physical and functional interactions have been demonstrated should be termed metabolons. We discuss the level of evidence for the manifold plant pathways that have been postulated to contain metabolons and then list examples in both primary and secondary metabolism for which strong evidence has been provided to support these claims. In doing so, we pay particular attention to experimental and mathematical approaches to study metabolons as well as complexities that arise in attempting to follow them. Finally, we discuss perspectives for improving our understanding of these fascinating but enigmatic interactions.http://www.sciencedirect.com/science/article/pii/S2590346220301048protein–protein interactionmetabolonsubstrate channeling
spellingShingle Youjun Zhang
Alisdair R. Fernie
Metabolons, enzyme–enzyme assemblies that mediate substrate channeling, and their roles in plant metabolism
Plant Communications
protein–protein interaction
metabolon
substrate channeling
title Metabolons, enzyme–enzyme assemblies that mediate substrate channeling, and their roles in plant metabolism
title_full Metabolons, enzyme–enzyme assemblies that mediate substrate channeling, and their roles in plant metabolism
title_fullStr Metabolons, enzyme–enzyme assemblies that mediate substrate channeling, and their roles in plant metabolism
title_full_unstemmed Metabolons, enzyme–enzyme assemblies that mediate substrate channeling, and their roles in plant metabolism
title_short Metabolons, enzyme–enzyme assemblies that mediate substrate channeling, and their roles in plant metabolism
title_sort metabolons enzyme enzyme assemblies that mediate substrate channeling and their roles in plant metabolism
topic protein–protein interaction
metabolon
substrate channeling
url http://www.sciencedirect.com/science/article/pii/S2590346220301048
work_keys_str_mv AT youjunzhang metabolonsenzymeenzymeassembliesthatmediatesubstratechannelingandtheirrolesinplantmetabolism
AT alisdairrfernie metabolonsenzymeenzymeassembliesthatmediatesubstratechannelingandtheirrolesinplantmetabolism