• If you are citizen of an European Union member nation, you may not use this service unless you are at least 16 years old.

  • Stop wasting time looking for files and revisions! Dokkio, a new product from the PBworks team, integrates and organizes your Drive, Dropbox, Box, Slack and Gmail files. Sign up for free.


Mitomycin C

Page history last edited by PBworks 12 years, 9 months ago

Mechanism of Action


Mitomycin C fucntions by crosslinking DNA.  A single crosslink per genome has shown to be effective in killing bacteria.  This is accomplished by reductive activation, followed, by a doulbe alkyation.  This process is very selective in that the first alkylation is at a guanine nucleoside in the sequence 5'-CpG-3' followed by a second alkylation at a site on the complimentary straand with the same sequence. 




I general the biosynthesis of all mitomycins proceed via combination of 3-amino-5-hydroxybenzoic acid (AHBA), D-glucosamine, and carbamoyl phosphate, to form the mitosane core, followed by specific tailoring steps.  The key intermediate, AHBA, is a common precursor to other anticancer drugs, such as rifamycin and ansamycin.


Specifially, the biosynthesis begins with the addition of phosphoenolpyruvate (PEP) to erythrose-4-phosphate (E4P) with a yet undiscovered enzyme, which is then ammoniated to give 4-amino-3-deoxy-D-arabino heptulosonic acid-7-phosphate (aminoDHAP).  Next, DHQ synthase catalyzes a ring closure to give 4-amino3-dehydroquinate (aminoDHQ), which is then undergoes a double oxidation via aminoDHQ dehydratase to give 4-amino-dehydroshikimate (aminoDHS).  The key intermediate, 3-amino-5-hydroxybenzoic acid (AHBA), is made via aromatization by AHBA synthase.


Figure 1.  Synthesis of the key intermediate, 3-amino-5-hydroxy-benzoic acid.



The mitosane core is synthesized via condensation of AHBA and D-glucosamine, although no specific enzyme has been characterized that mediates this transformation.  Once this condensation has occurred, the mitosane core is tailored by a variety of enzymes.  Unfortunately, both the sequence and the identity of these steps are yet to be determined.



·        Complete reduction of C-6

o       Likely via F420-dependent tetrahydromethanopterin (H4MPT)) reductase and H4MPT:CoM methyltransferase


·        Hydroxylation of C-5, C-7 (followed by transamination), and C-9a.

o       Likely via cytochrome P450 monooxygenase or benzoate hydroxylase


·        O-Methylation at C-9a

o       Likely via SAM dependent methyltransferase


·        Oxidation at C-5 and C8

o       Unknown


·        Intramolecular amination to form aziridine

o       Unknown


·        Carbamoylation at C-10

o       Carbamoyl transferrase, with carbamoyl phosphate (C4P) being derived from L-citrulline or L-arginine


 Figure 2.  Formatoin of mitosane core followed by tailoring specific to Mitomycin C.



Comments (0)

You don't have permission to comment on this page.