Dataset Information

Cellular compartmentalization of secondary metabolism.

ABSTRACT: Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g., amino acids, acetyl CoA, NADPH), enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported.

SUBMITTER: Kistler HC

PROVIDER: S-EPMC4321598 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Cellular compartmentalization of secondary metabolism.

Kistler H Corby HC Broz Karen K

Frontiers in microbiology 20150209

Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g., amino acids, acetyl CoA, NADPH), enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position ...[more]

PMID: 25709603

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Project description:Biochemical regulation in compartmentalized metabolic networks is highly complex and non-intuitive. This is particularly true for cells of higher plants showing one of the most compartmentalized cellular structures across all kingdoms of life. The interpretation and testable hypothesis generation from experimental data on such complex systems is a challenging step in biological research and biotechnological applications. While it is known that subcellular compartments provide defined reaction spaces within a cell allowing for the tight coordination of complex biochemical reaction sequences, its role in the coordination of metabolic signals during metabolic reprogramming due to environmental fluctuations is less clear. In the present study, we numerically analysed the effects of environmental fluctuations in a subcellular metabolic network with regard to the stability of an experimentally observed steady state in the genetic model plant Arabidopsis thaliana. Applying a method for kinetic parameter normalization, several millions of probable enzyme kinetic parameter constellations were simulated and evaluated with regard to the stability information of the metabolic homeostasis. Information about the stability of the metabolic steady state was derived from real parts of eigenvalues of Jacobian matrices. Our results provide evidence for a differential stabilizing contribution of different subcellular compartments. We could identify stabilizing and destabilizing network components which we could classify according to their subcellular localization. The findings prove that a highly dynamic interplay between intracellular compartments is preliminary for an efficient stabilization of a metabolic homeostasis after environmental perturbation. Further, our results provide evidence that feedback-inhibition originating from the cytosol and plastid seem to stabilize the sucrose homeostasis more efficiently than vacuolar control. In summary, our results indicate stabilizing and destabilizing network components in context of their subcellular organization.

Dataset Information

Cellular compartmentalization of secondary metabolism.

Publications

Cellular compartmentalization of secondary metabolism.

Similar Datasets

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