Reaction: 2 ATP + 2 (indol-3-yl)pyruvate = 2 AMP + 2 diphosphate + didemethylasterriquinone D (overall reaction)
(1a) ATP + (indol-3-yl)pyruvate + [didemethylasterriquinone D synthase] = AMP + diphosphate + (indol-3-yl)pyruvoyl-[didemethylasterriquinone D synthase]
(1b) ATP + (indol-3-yl)pyruvate + (indol-3-yl)pyruvoyl-[didemethylasterriquinone D synthase] = AMP + diphosphate + didemethylasterriquinone D + [didemethylasterriquinone D synthase]
Glossary: didemethylasterriquinone D = 3,6-dihydroxy-2,5-diindol-3′-yl-1,4-benzoquinone
Other name(s): didemethylasterriquinone D synthetase; tdiA (gene name)
Systematic name: (indol-3-yl)pyruvate:(indol-3-yl)pyruvate ligase (didemethylasterriquinone D-forming)
Comments: Requires Mg2+. The enzyme, characterized from the fungus Aspergillus nidulans, is a non-ribosomal peptide synthase-like enzyme comprising three domains - an adelylation (A) domain, an ayl-carrier protein (ACP) domain, and a thioesterase (TE) domain. The enzyme activates (indol-3-yl)pyruvate by adenylation and catalyses the dimerization/cyclization of two such molecules to form didemethylasterriquinone D. didemethylasterriquinone D is subsequently converted to terrequinone A, a cytotoxic compound that displays a broad range of bioactivities.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Bok, J.W., Hoffmeister, D., Maggio-Hall, L.A., Murillo, R., Glasner, J.D. and Keller, N.P. Genomic mining for Aspergillus natural products. Chem. Biol. 13 (2006) 31-37. [PMID: 16426969]
2. Schneider, P., Weber, M., Rosenberger, K. and Hoffmeister, D. A one-pot chemoenzymatic synthesis for the universal precursor of antidiabetes and antiviral bis-indolylquinones. Chem. Biol. 14 (2007) 635-644. [PMID: 17584611]
3. Balibar, C.J., Howard-Jones, A.R. and Walsh, C.T. Terrequinone A biosynthesis through L-tryptophan oxidation, dimerization and bisprenylation. Nat. Chem. Biol. 3 (2007) 584-592. [PMID: 17704773]