TY - JOUR
T1 - Characterization of TioF, a tryptophan 2,3-dioxygenase involved in 3-hydroxyquinaldic acid formation during thiocoraline biosynthesis
AU - Sheoran, Anita
AU - King, Andrew
AU - Velasco, Ana
AU - Pero, Jessica M.
AU - Garneau-Tsodikova, Sylvie
PY - 2008
Y1 - 2008
N2 - Thiocoraline is a thiodepsipeptide antitumor agent that belongs to the family of bisintercalator natural products that bind duplex DNA through their two planar intercalating moieties. In thiocoraline, the 3-hydroxyquinaldic acid (3HQA) chromophores required for intercalation are derived from l-Trp. We have expressed the Micromonospora sp. ML1 tryptophan 2,3-dioxygenase (TDO) TioF, purified it from E. coli, and confirmed its role in the irreversible oxidation of l-Trp to N-formylkynurenine, the proposed first step during 3HQA biosynthesis. We have established that TioF is a catalyst with broader specificity than other TDOs, but that is less promiscuous than indoleamine 2,3-dioxygenases. TioF was found to display activity with various l-Trp analogs (serotonin, d-Trp, and indole). The TioF reaction products generated during this study will be used as substrates for subsequent analysis of the other enzymes involved in 3HQA biosynthesis.
AB - Thiocoraline is a thiodepsipeptide antitumor agent that belongs to the family of bisintercalator natural products that bind duplex DNA through their two planar intercalating moieties. In thiocoraline, the 3-hydroxyquinaldic acid (3HQA) chromophores required for intercalation are derived from l-Trp. We have expressed the Micromonospora sp. ML1 tryptophan 2,3-dioxygenase (TDO) TioF, purified it from E. coli, and confirmed its role in the irreversible oxidation of l-Trp to N-formylkynurenine, the proposed first step during 3HQA biosynthesis. We have established that TioF is a catalyst with broader specificity than other TDOs, but that is less promiscuous than indoleamine 2,3-dioxygenases. TioF was found to display activity with various l-Trp analogs (serotonin, d-Trp, and indole). The TioF reaction products generated during this study will be used as substrates for subsequent analysis of the other enzymes involved in 3HQA biosynthesis.
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U2 - 10.1039/b801391h
DO - 10.1039/b801391h
M3 - Article
C2 - 18493661
AN - SCOPUS:43949096904
SN - 1742-206X
VL - 4
SP - 622
EP - 628
JO - Molecular BioSystems
JF - Molecular BioSystems
IS - 6
ER -