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Advantages of the Enzyme Route
The enzyme is completely stereo selective. This means that it is possible to use either a racemic mixture or the L-isomer of the substrate.

None of the bitter isomer of aspartame is produced.

The reaction takes place under mild conditions

  • pH: 7.0 -7.5
  • Temperature: 500c
  • In aqueous solution

After the enzyme reaction there is further chemical processing to remove protecting groups, and to convert the methyl ester to aspartame itself.

Reaction Scheme for Aspartame Manufacture
diagram: reaction scheme for aspartame manufacture
X is a protecting group removed at the end


What change(s) do you think are caused by the use of HCl?

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The enzyme employed is called thermolysin found in the bacterial strain Bacillus proteolicus/ thermoproteolyticus in the Rokko Hot Spring in Japan. The enzyme is stable up to temperatures of 60oC. It is extracted and used in a form soluble in water in a process started in 1988.

The reaction is limited by the equilibrium position, and so products have to be removed from the mixture in order to achieve high yields.