Caffeine Pathway Map (fungal)

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This pathway was contributed by Rachael Long and Tony Dodge, University of Minnesota.

Caffeine (1,3,7-trimethylxanthine) is found naturally in coffee, tea and cocoa and used as a food and drug additive. When ingested by humans, caffeine stimulates the central nervous system, elevates blood pressure, increases metabolic rate, and acts as a diuretic (Higdon and Frei, 2006). Caffeine consumption may reduce the risk of Parkinson's disease. However, adverse reactions to caffeine consumption can include anxiety, insomnia, heart palpitations, abdominal pain, and nausea, and high caffeine intake has been linked with increased risk of osteoporosis and complications in pregnancy (Dash and Gummadi, 2006). Caffeine is also mildly addictive. Withdrawal symptoms can include headache, fatigue, depressed mood, difficulty concentrating, irritability, nausea, and muscle pain (Higdon and Frei, 2006).

Coffee pulp, a waste product produced during coffee processing, is a major pollutant in water bodies near coffee plants. Even though it is high in nutrients, it cannot be used as animal feed due to the high levels of caffeine and other unwanted compounds (Pandey et al., 2000). Solvents commonly used to produce caffeine-free products are either very expensive to use or toxic (Dash and Gummadi, 2006). However, a number of bacterial and fungal strains capable of degrading caffeine have been identified (Mazzafera, 2004).

The pathway described below has been documented for members of the fungal species Penicillium commune and Aspergillus tamarii (Hakil et al. 1998. Enzyme Microb Technol 22: 355-359), other members of these two genera, and the bacterial species Pseudomonas putida CBB5 (Yu et al., 2009). In the major fungal pathway, caffeine degrades via theophylline (1,3-dimethylxanthine) and 3-methylxanthine to xanthine. Bacterial and minor fungal pathway branches funnel through paraxanthine and theobromine. In contrast to other known bacterial pathways, no methyluric acids are reported as degradation products.

The following is a text-format caffeine degradation pathway map. Organisms which can initiate the pathway are given, but other organisms may also carry out later steps. Follow the links for more information on compounds or reactions. This map is also available in graphic (13k) format.

                                                               Caffeine
                                                       Pseudomonas putida CBB5
                                                         Penicillium commune 
                                                         Aspergillus tamarii
                                                              and others
                                                                  |
                                                                  |  
                                                                  | 
                                                                  |
                           +--------------------------------------+----------------------------+
                           |                                      |                            | 
                           | caffeine                             | caffeine                   | caffeine 
                           | demethylase                          | demethylase                | demethylase
                           |                                      |                            |
                           |                                      |                            | 
                           v                                      v                            v 
                      Paraxanthine                           Theophylline                 Theobromine
                           |                                      |                            |  
                           |                                      |                            |
                           |                                      |                            | 
                   +-------+---------+                 +----------+----------+                 |  
                   |                 |                 |                     |                 |
                   |                 |                 |                     |                 |
                   | paraxanthine    | paraxanthine    | theophylline        | theophylline    | theobromine
                   | demethylase     | demethylase     | demethylase         | demethylase     | demethylase
                   |                 |                 |                     |                 |              
                   v                 v                 v                     v                 v
            7-Methylxanthine           1-Methylxanthine                        3-Methylxanthine           
                   |                          |                                        |   
                   |                          |                                        |                  
                   |                          |                                        |               
                   | heteroxanthine           | heteroxanthine                         | heteroxanthine                    
                   | demethylase              | demethylase                            | demethylase                                
                   |                          |                                        |                     
                   |                          |                                        |                            
                   |                          |                                        |                             
                   +--------------------------+--------------> Xanthine <--------------+ 	  
                                                                  |                                         
                                                                  | 
                                                                  | 
                                                                  | 
                                                                  | 
                                                                  v
                                                             Intermediary
                                                              Metabolism
                                                                (KEGG)


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Page Author(s): Rachael Long

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