The amino acid L-serine is synthesized by a simple three step pathway using 3-phospho-D-glycerate (3PG) as the starting substrate. If L-serine is available in the cell surroundings, E. coli prefers to import it rather than synthesize it. By doing do, the cell conserves energy and carbon intermediates for other needs.

The overall L-serine pathway formula is:

3-phospho-D-glycerate + phosphate + NADH + H+ + L-glutamate + H2O → L-serine + NAD+ + 2-oxoglutarate

Key Concepts

  • E. coli synthesizes L-serine in three steps starting with the biosynthetic precursor, 3-phospho-D- glycerate (3PG).
  • Cells also acquire L-serine from the surrounding environment using one of three transport systems.
  • L-serine is a biosynthetic precursor of several other cell building blocks, the amino acids L-glycine and L-cysteine, and several lipids.
  • As one of the 21 amino acids present in proteins, cells require large amounts of L-serine for cell growth.


E. coli requires relatively large amounts of L-serine since it constitutes roughly 5-6% of the amino acids that make up a typical cell protein. L-serine is also needed as a starting product to synthesize several other amino acids, glycine, cysteine, and tryptophan in addition to certain lipids

E. coli synthesizes L-serine from one of the twelve cell building blocks, 3-phospho-D-glycerate (3PG). (3PG). Cells also scavenge L-serine molecules from the cell environments by one or more dedicated nutrient uptake systems that differ in molecule specificity and affinity.

I. The pathway for L-serine synthesis from 3-phospho-D-glycerate

This short biosynthetic pathway is composed of three reactions. The starting product is derived from breakdown of glucose by the glycolysis pathway or synthesized by the gluconeogenesis pathway.

  1. D-3-phosphoglycerate dehydrogenase (SerA)       
  2. 3-phosphoserine aminotransferase (SerC)       
  3. phosphoserine phosphatase (SerB)       

II. Uptake of L-serine across the cell membrane

L-serine can be acquired from the cell surroundings by one of three distinct nutrient uptake systems named SdaC, ScdC, and SstT. They differ in substrate specificity and in their affinity for L-serine.

III. Regulation of L-serine biosynthesis and transport

E. coli cells are economical in conserving carbon and energy. E. coli accomplishes this in part by regulating L-serine production via a combination of gene and protein controls. An overview is provided below.

Transcriptional control by activation/repression

Expression of the serA gene encoding the first enzyme of the pathway, D-3-phosphoglycerate dehydrogenase, is transcriptionally regulated by the Nac and Lrp dual regulators. The molecular details are not fully understood.

Feedback control of enzyme activity

The first enzyme of the pathway, D-3-phosphoglycerate dehydrogenase (SerA), is inhibited by the end product, L-serine. If L-serine levels in the cell are reduced due to its consumption during protein synthesis, the enzyme activity is restored.


  • The essential amino acid L-serine is synthesized in three steps.
  • L-serine is needed for protein synthesis, lipid synthesis, and for making several other amino acids.
  • Several dedicated active transport systems are used to acquire it when present in the cell surroundings.
  • Cells control the synthesis of L-serine by several mechanisms.



Authored by Robert Gunsalus and Imke Schröder
©The Escherichia coli Student Portal

This project acknowledges support from:
NIH Grant Award GM077678 to SRI, International
Peter Karp and coworkers at EcoCyc.org
The UCLA Department of MIMG