Chapter 17 Bacterial Fatty Acid Synthesis and its Relationships with Polyketide Synthetic Pathways

Abstract

This review presents the most thoroughly studied bacterial fatty acid synthetic pathway, that of Escherichia coli and then discusses the exceptions to the E. coli pathway present in other bacteria. The known interrelationships between the fatty acid and polyketide synthetic pathways are also assessed, mainly in the Streptomyces group of bacteria. Finally, we present a compendium of methods for analysis of bacterial fatty acid synthetic pathways.

Suppression of fabB Mutation by fabF1 Is Mediated by Transcription Read-through in Shewanella oneidensis

“…1). In E. coli, on which the current understanding of the pathway and its constituents is largely built, KAS enzymes (FabB, FabF, and FabH) that catalyze 3-ketoacyl-ACP synthase reactions have been extensively studied (1). Both FabB and FabF participate in elongation of longchain acyl-ACP in both arms to control fatty acid composition and impact the rate of fatty acid production (3,4,34,37).…”

“…he de novo fatty acid synthesis (FAS) pathway, namely, type II, is the predominant, if not exclusive, route for endogenous production of fatty acids (1). The FAS pathway, the current knowledge of which derives mainly from the model organism Escherichia coli, is highly conserved in bacteria.…”

“…Central to the pathway are reactions catalyzed by ␤-ketoacyl-acyl carrier protein (ACP) synthases (KAS), including FabH, FabB, and FabF. FabH is responsible for the condensation of an acyl coenzyme A (acylCoA) unit and a malonyl-acyl carrier protein (malonyl-ACP) unit, but cannot work with acetyl-ACP, the substrate of FabB and FabF; as a consequence, FabH could not function as a replacement for FabB or FabF (1). While FabB and FabF are exchangeable in elongation of saturated intermediates, each catalyzes a reaction with the unsaturated branch that the other cannot or at least much less effectively (2) (Fig.…”

Carboxylases in Natural and Synthetic Microbial Pathways

“…In both biosynthetic pathways, ␣-carboxylations are used to provide activated acylCoA ester building blocks for subsequent carbon-carbon bondforming reactions (see Fig. S8 in the supplemental material) (32).…”

“…As seen with fatty acid synthases, the phylogenetically related polyketide synthases use ␣-carboxyl-thioesters as extender units (32). In order to vary the molecule backbone, however, polyketide synthases make use of other extender units in addition to malonyl-CoA.…”