Adamantanone Pathway Map

Oxygenated adamantanes such as hydroxylated adamantanone have recently shown to possess promising immunomodulating and other useful properties. Adamantanone is hydroxylated by purified cytochrome P-450_CAM, the camphor hydroxylating component of soluble camphor monooxygenase from Pseudomonas putida ATCC 17453. After growth in media with camphor as sole carbon and energy source, washed cells were capable of transforming adamantanone into number of metabolites. Microbial metabolism of adamantanone (tricyclo[3.3.1^3,7]decan-2-one) is documented by Selifonov (1992). The potential of such organisms in the biotransformation and production of specialty chemicals however has not yet been fully explored. Hydroxylated and non-hydroxylated adamantane lactones, compounds of potential pharmaceutical and synthetic interest, can be easily obtained using the same biocatalyst, cells of the P.putida, in a "one pot synthesis" in essentially quantitative yield.

Biotransformation pathways for adamantanone in P.putida strain PpG1 (ATCC 17453) can be proposed as shown in the pathway map. Two divergent reactions of adamantanone oxidation are apparently provided by enzymes responsible for the initial steps of camphor catabolism: camphor 5-monooxygenase(P-450_CAM) and camphor 1,2-monooxygenase, a NADH-dependent two-component cycloalkanone monooxygenase, leading to formation of 5-hydroxyadamantan-2-one and 4-oxahomoadamantan-5-one, respectively. Cytochrome P-450_CAM in cell-free experiments has been shown to catalyze the formation of 5-hydroxyadamantan-2-one from adamantanone. However, camphor 1,2-monooxygenase appears to be the first enzyme shown to perform biological Baeyer-Villiger reaction with adamantanone. Further conversion of compounds to hydroxylactone are evidently mediated by camphor 1,2-monooxygenase and camphor 5-monooxygenase both recognizing these adamantane derivatives as substrate analogs of camphor. The hydroxylactone 1-hydroxy-4-oxahomoadamantan-5-one accumulates, although this organism can hydrolyze the camphor lactone.

The following is a text-format adamantanone 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 (10k) format.

                          Adamantanone
              Pseudomonas putida PpG1 (ATCC 17453)
                               |                              
                              / \         
                  camphor 5- /   \ camphor 1,2-
              monooxygenase /     \ monooxygenase
                           /       \
                          /         \
                         /           \               
                        v             v                                  
               5-Hydroxy-            4-Oxahomo-              
            adamantan-2-one        adamantan-5-one     
                         \           /
                          \         /
              camphor 1,2- \       / camphor 5-
              monooxygenase \     / monooxygenase
                             \   /
                              \ /
                               |
                               v
               1-Hydroxy-4-oxahomoadamantan-5-one
                     
         

Page Author(s): Jenny Kang

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