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Stereochemical Insights into the Anaerobic Degradation of 4‐Isopropylbenzoyl‐CoA in the Denitrifying Bacterium Strain pCyN1
Author(s) -
Küppers Julian,
Becker Patrick,
Jarling René,
Dörries Marvin,
Cakić Nevenka,
Schmidtmann Marc,
Christoffers Jens,
Rabus Ralf,
Wilkes Heinz
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201805837
Subject(s) - carboxylate , chemistry , stereochemistry , isopropyl , hydroxylation , stereocenter , medicinal chemistry , stereoselectivity , organic chemistry , catalysis , enantioselective synthesis , enzyme
The constitutions and absolute configurations of two previously unknown intermediates, (1 S ,2 S ,4 S )‐2‐hydroxy‐4‐isopropylcyclohexane‐1‐carboxylate and ( S )‐3‐isopropylpimelate, of anaerobic degradation of p ‐cymene in the bacterium Aromatoleum aromaticum pCyN1 are reported. These intermediates (as CoA esters) are involved in the further degradation of 4‐isopropylbenzoyl‐CoA formed by methyl group hydroxylation and subsequent oxidation of p ‐cymene. Proteogenomics indicated 4‐isopropylbenzoyl‐CoA degradation involves (i) a novel member of class I benzoyl‐CoA reductase (BCR) as known from Thauera aromatica K172 and (ii) a modified β‐oxidation pathway yielding 3‐isopropylpimeloyl‐CoA analogously to benzoyl‐CoA degradation in Rhodopseudomonas palustris . Reference standards of all four diastereoisomers of 2‐hydroxy‐4‐isopropylcyclohexane‐1‐carboxylate as well as both enantiomers of 3‐isopropylpimelate were obtained by stereoselective syntheses via methyl 4‐isopropyl‐2‐oxocyclohexane‐1‐carboxylate. The stereogenic center carrying the isopropyl group was established using a rhodium‐catalyzed asymmetric conjugate addition. X‐ray crystallography revealed that the thermodynamically most stable stereoisomer of 2‐hydroxy‐4‐isopropylcyclohexane‐1‐carboxylate is formed during p ‐cymene degradation. Our findings imply that the reductive dearomatization of 4‐isopropylbenzoyl‐CoA by the BCR of A. aromaticum pCyN1 stereospecifically forms ( S )‐4‐isopropyl‐1,5‐cyclohexadiene‐1‐carbonyl‐CoA.