Kan SB. J.
Huang X.
Gumulya Y.
Chen K.
Arnold FH.
* California Institute of Technology, Pasadena, USA
Genetically Programmed Chiral Organoborane Synthesis.
Nature 2017;
552: 132-136
Key words
organoboranes - carbenoid insertion - mutagenesis - directed evolution
Significance
The Arnold group reports a whole-cell-catalyzed organoboron synthesis through carbenoid
B–H insertion. Identification of an appropriate boron reagent that is stable and active
under physiological conditions and site-saturation mutagenesis of the wild-type cytochrome
c from Rodothermus marinus to afford a series of Escherichia coli cells that catalyze the desired transformation permitted the synthesis to be performed
with remarkable turnover numbers and enantioselectivities. Interestingly, lower turnover
frequencies were obtained by using either purified protein or cell lysate. Turnover
numbers could be increased up to 15300 TTN by portionwise addition of substrates.
Comment
Chiral organoboron compounds are versatile synthetic intermediates, and therefore
their asymmetric synthesis is of great interest. However, no organism is known to
form the desired C–B bond. As a continuation of their previous work on enzyme-catalyzed
carbenoid insertions (Science 2016, 354, 1048), the authors again impressively demonstrate that selective DNA modification
can produce microorganisms that are able to achieve this unnatural bond formation
in high efficiency (up to 400 times more active than published metal-catalyzed systems)
and with high selectivity.
