Structure, stereochemistry and synthesis of enantiopure cyclohexenone cis-diol bacterial metabolites derived from phenols

Oxidative biotransformations of phenol substrates catalysed by toluene dioxygenase: A molecular docking study

“…It was noted that, within the TDO active site, the meta-position of bound toluene was very close to the imidazole ring of His-311. This observation led to the proposal, that an attractive interaction between the acidic OH group of meta-phenol substrates and the basic imidazole ring, could explain the observed regio-and stereo-selective dihydroxylation of phenolic substrates, to yield cisdihydrodiols B and H and the preferred ketotautomers F and G [7][8][9][10][11]. Conversely, the TDO-catalysed cisdihydroxylation was inhibited by the presence of an alkyl group at the meta-position of non-phenolic disubstituted benzene substrates, e.g.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Thus, toluene dioxygenase (TDO) [2,3,[7][8][9][10][11], naphthalene dioxygenase (NDO) [9,12], biphenyl dioxygenase (BPDO) [9,12,13] and o-xylene dioxygenase (OXDO) [14] have all been used to catalyse the formation of catechols B, as major metabolites of phenols A. To date, the binding interactions of phenolic substrates with amino acid residues at the active site of RHDs are relatively unexplored.…”

“…Recent reports showed that, in many cases, catechols B were accompanied by a new family of cyclohex-2-en-1-one cis-diols, as major metabolites (F and G) [7][8][9][10][11]13]. Biotransformations of phenols, with the TDO-expressing constitutive mutant Pseudomonas putida UV4 and recombinant strain Escherichia coli p-CL-4t, resulted in more than twenty cyclohex-2-en-1-one cis-diols (F and G) being added to this new family of metabolites [7][8][9][10][11].…”

“…TDO-catalysed hydroxylation mechanisms have been postulated to account for: (a) the formation of benzene-1,2-diols (catechols, D) via triol intermediates (C) [3], (b) benzene-1,4-diols (hydroquinones, E) [11,14] and (c) cyclohex-2-en-1-one cis-diols (F and G) via cis-dihydrodiol metabolites (B and H) [7][8][9][10][11]13] (Scheme 1). While the dehydration of cyclohex-2-en-1-onecis-diols F and G, to yield hydroquinones E, was observed in the presence of acid and occurred during biotransformations, neither triol C nor cisdihydrodiol intermediates B and H were detected.…”

“…Biotransformations of phenols, with the TDO-expressing constitutive mutant Pseudomonas putida UV4 and recombinant strain Escherichia coli p-CL-4t, resulted in more than twenty cyclohex-2-en-1-one cis-diols (F and G) being added to this new family of metabolites [7][8][9][10][11]. Hydroquinones E were also detected as minor phenol derivatives using bacteria expressing TDO [7][8][9][10][11], NDO [12], BPDO [12]and OXDO [14].…”