1385844-63-2Relevant academic research and scientific papers
Stereochemical outcome at four stereogenic centers during conversion of prephenate to tetrahydrotyrosine by BacABGF in the bacilysin pathway
Parker, Jared B.,Walsh, Christopher T.
, p. 5622 - 5632 (2012)
The first four enzymes of the bacilysin antibiotic pathway, BacABGF, convert prephenate to a tetrahydrotyrosine (H4Tyr) diastereomer on the way to the anticapsin warhead of the dipeptide antibiotic. BacB takes the BacA product endocyclic-Δ4,Δ8-7R- dihydrohydroxyphenylpyruvate (en-H2HPP) and generates a mixture of 3E- and 3Z-olefins of the exocyclic-Δ3,Δ5- dihydrohydroxyphenylpyruvate (ex-H2HPP). The NADH-utilizing BacG then catalyzes a conjugate reduction, adding a pro-S hydride equivalent to C 4 to yield tetrahydrohydroxyphenylpyruvate (H4HPP), a transamination away (via BacF) from 2S-H4Tyr. Incubations of the pathway enzymes in D2O yield deuterium incorporation at C8 from BacA and then C9 from BacB action. By 1H NMR analysis of samples of H4Tyr, the stereochemistry at C4, C8, and C9 can be assigned. BacG (followed by BacF) converts 3E-ex-H2HPP to 2S,4R,7R-H4Tyr. The 3Z isomer is instead reduced and transaminated to the opposite diastereomer at C4, 2S,4S,7R-H4Tyr. Given that bacilysin has the 2S,4S stereochemistry in its anticapsin moiety, it is likely that the 2S,4S-H4Tyr is the diastereomer "on pathway". NMR determination of the stereochemistry of the CHD samples at C8 and C9 allows assignment of all stereogenic centers (except C3) in this unusual tetrahydro-aromatic amino acid building block, giving insights into and constraints on the BacA, BacB, and BacG mechanisms.
