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Regulation of cell size in response to nutrient availability by fatty acid biosynthesis in Escherichia coli.

ABSTRACT: Cell size varies greatly among different types of cells, but the range in size that a specific cell type can reach is limited. A long-standing question in biology is how cells control their size. Escherichia coli adjusts size and growth rate according to the availability of nutrients so that it grows larger and faster in nutrient-rich media than in nutrient-poor media. Here, we describe how, using classical genetics, we have isolated a remarkably small E. coli mutant that has undergone a 70% reduction in cell volume with respect to wild type. This mutant lacks FabH, an enzyme involved in fatty acid biosynthesis that previously was thought to be essential for the viability of E. coli. We demonstrate that although FabH is not essential in wild-type E. coli, it is essential in cells that are defective in the production of the small-molecule and global regulator ppGpp. Furthermore, we have found that the loss of FabH causes a reduction in the rate of envelope growth and renders cells unable to regulate cell size properly in response to nutrient excess. Therefore we propose a model in which fatty acid biosynthesis plays a central role in regulating the size of E. coli cells in response to nutrient availability.

SUBMITTER: Yao Z

PROVIDER: S-EPMC3458391 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Regulation of cell size in response to nutrient availability by fatty acid biosynthesis in Escherichia coli.

Yao Zhizhong Z Davis Rebecca M RM Kishony Roy R Kahne Daniel D Ruiz Natividad N

Proceedings of the National Academy of Sciences of the United States of America 20120820 38

Cell size varies greatly among different types of cells, but the range in size that a specific cell type can reach is limited. A long-standing question in biology is how cells control their size. Escherichia coli adjusts size and growth rate according to the availability of nutrients so that it grows larger and faster in nutrient-rich media than in nutrient-poor media. Here, we describe how, using classical genetics, we have isolated a remarkably small E. coli mutant that has undergone a 70% red ...[more]

PMID: 22908292

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Project description:Type II fatty acid biosynthesis in bacteria can be broadly classified into the initiation and elongation phases. The biochemical functions defining each step in the two phases have been studied in vitro Among the ?-ketoacyl-acyl carrier protein (ACP) synthases, FabH catalyzes the initiation reaction, while FabB and FabF, which primarily catalyze the elongation reaction, can also drive initiation as side reactions. A role for FabB and FabF in the initiation of fatty acid biosynthesis would be supported by the viability of the ?fabH mutant. In this study, we show that the ?fabH and ?yiiD mutations were synthetically lethal and that ?fabH ?relA ?spoT and ?fabH ?dksA synthetic lethality was rescued by the heterologous expression of yiiD In the ?fabH mutant, the expression of yiiD was positively regulated by (p)ppGpp. The growth defect, reduced cell size, and altered fatty acid profile of the ?fabH mutant and the growth defect of the ?fabH ?fabF fabB15(Ts) mutant in oleate- and palmitate-supplemented medium at 42°C were rescued by the expression of yiiD from a multicopy plasmid. Together, these results indicate that the yiiD-encoded function supported initiation of fatty acid biosynthesis in the absence of FabH. We have renamed yiiD as fabY IMPORTANCE Fatty acid biosynthesis is an essential process conserved across life forms. ?-Ketoacyl-ACP synthases are essential for fatty acid biosynthesis. FabH is a ?-ketoacyl-ACP synthase that contributes to the initiation of fatty acid biosynthesis in Escherichia coli In this study, we present genetic and biochemical evidence that the yiiD (renamed fabY)-encoded function contributes to the biosynthesis of fatty acid in the absence of FabH activity and that under these conditions, the expression of FabY was regulated by the stringent response factors (p)ppGpp and DksA. Combined inactivation of FabH and FabY resulted in growth arrest, possibly due to the loss of fatty acid biosynthesis. A molecule(s) that inhibits the two activities can be an effective microbicide.

Dataset Information

Regulation of cell size in response to nutrient availability by fatty acid biosynthesis in Escherichia coli.

Publications

Regulation of cell size in response to nutrient availability by fatty acid biosynthesis in Escherichia coli.

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