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Pathway · 4 proteins

Fatty-acid elongation

Condensation, reduction and dehydration extend acyl chains.

How it works

  1. Elongation is a four-reaction cycle: condensation of an acyl-ACP with malonyl-ACP by a beta-ketoacyl-ACP synthase, reduction of the beta-keto group, dehydration, and reduction of the enoyl intermediate.
  2. VF5 carries a FabH-type synthase for the first round and a FabF-type synthase for later rounds, together with FabZ dehydratase and FabI enoyl-ACP reductase. That is the dissociated type II system, not a single multifunctional synthase.
  3. Each round adds two carbons and consumes NADPH. The annotations name the enzymes but not the chain-length distribution, which depends on which synthase acts and on competing acyltransferases in the modules below.

Grouped by the atlas’s curated pathway map. The table order is not a proven reaction order.

Its proteins

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
3-hydroxyacyl-[acyl-carrier-protein] dehydratase FabZ4.2.1.59a (3R)-hydroxyacyl-[ACP] = a (2E)-enoyl-[ACP] + H2O—150Step named
Beta-ketoacyl-[acyl-carrier-protein] synthase III2.3.1.180malonyl-[ACP] + acetyl-CoA + H(+) = 3-oxobutanoyl-[ACP] + CO2 + CoA—309Step named
Enoyl-[acyl-carrier-protein] reductase [NADH] FabI1.3.1.9a 2,3-saturated acyl-[ACP] + NAD(+) = a (2E)-enoyl-[ACP] + NADH + H(+)—270Step named
3-oxoacyl-[acyl-carrier-protein] synthase 22.3.1.179(9Z)-hexadecenoyl-[ACP] + malonyl-[ACP] + H(+) = 3-oxo-(11Z)-octadecenoyl-[ACP] + holo-[ACP] + CO2—415Step named

Origins

Could long fatty-acid chains have formed before the enzymes that build them two carbons at a time?

Naturalistic proposal

Organic chemists have made fatty-acid chains under strenuous conditions, and saturated hydrocarbons under milder conditions with the help of iron sulfide. Zubay describes a proposed prebiotic route that resembles the biosynthetic one.

Design analysis

In the cell, chains grow on the acyl carrier protein by a repeated cycle of four reactions, and every round needs an activated two-carbon unit made with ATP. Four proteins in this group drive the cycle.

From the books: Zubay, Origins of Life on Earth and in the Cosmos, pp. 331 and 336; Ribas de Pouplana (ed.), The Genetic Code and the Origin of Life, p. 67.

The wider question for this part of the cell: origins for building and maintaining the membrane.

Sources

Other pathways in this group: Glycerolipid assembly · Lipid A and outer envelope · Substrate recognition · Terpenoid backbone biosynthesis · Fatty acid biosynthesis · Lipopolysaccharide biosynthesis · Biosynthesis of various nucleotide sugars · Not yet placed in a pathway