Commercial Production of
What is citric acid?
• Citric acid is a 6 carbon tricarboxylic acid.
Citric Acid Production
• Citric acid is widely used in the food
industry as an acidifier and antioxidant.
• It also has use as an environmentally
friendly and biodegradable cleaner
• It serves as a metal chelator in the lab
• About 300,000,000 kg are produced
annually worldwide, almost all of it (>90 %)
from aerobic fermentation of Aspergillus
Costs and Manufacture
• A commodity chemical, citric acid sells for less
than $1.00/lb, perhaps as low as $1.00/kg.
• The media used to produce CA is typically
derived from a low cost sugar source, most
typically sugar cane waste streams or partially
– (Divalent ions (Fe, Mn, Zn,Cu) play important roles in
CA production and typically must be removed from
these crude media before fermentation)
• Citric acid is found in almost all living
• CA is a component of the TCA cycle.
– Formed from the condensation of oxalacetate
(OAA) with AcetylCoA.
– Normally CA is then converted to CO2 by
passing through the TCA cycle (next slide)
• In high producing lines of A. niger, several things
conspire to force high production of CA.
– First, the isomerization of CA to isocitrate is slowed by lack of
Fe+2 ions, which inhibits the enzyme aconitase.
– Second, isocitrate dehydrogenase, the enzyme catalyzing
conversion of isocitrate to a-oxoglutarate is inhibited by high
– Third, a-oxoglutarate dehydrogenase (a-oxoglutarate to succinyl
CoA) is inhibited by high glucose levels in the media.
These factors contribute to a blockage of metabolism at the citrate
step and accumulation and excretion of citrate.
• At high pH (>4) oxaloacetate is broken down
(undesirable) to acetate and oxalic acid. This
makes it unavailable for CA formation. Low pH
(~2) limits this reaction
• In order to produce the intermediates of the TCA
cycle needed for cell growth and maintenance,
cell produces OAA by one of two other routes
and “runs the TCA cycle backwards” to supply
malate, fumarate, succinate, and succinyl CoA
to the cells.