A catalytically active [Mn]-hydrogenase incorporating a non-native metal cofactor

Abstract

Nature carefully selects specific metal ions for incorporation into the enzymes that catalyze the chemical reactions necessary for life. Hydrogenases, enzymes that activate molecular H2, exclusively utilize Ni and Fe in [NiFe]-, [FeFe]-, and [Fe]-hydrogeanses. However, other transition metals are known to activate or catalyze the production of hydrogen in synthetic systems. Here, we report the development of a biomimetic model complex of [Fe]-hydrogenase that incorporates a Mn, as opposed to a Fe, metal center. This Mn complex is able to heterolytically cleave H2 as well as catalyze hydrogenation reactions. Incorporation of the model into an apoenzyme of [Fe]-hydrogenase results in a [Mn]-hydrogenase with enhanced occupancy-normalized activity over an analogous semi-synthetic [Fe]-hydrogenase. These findings represent the first instance of a non-native metal hydrogenase showing catalytic functionality and demonstrate that hydrogenases based on a manganese active site are viable.

Biomimetic Hydrogenation Catalyzed by a Manganese Model of [Fe]‐Hydrogenase

“…The mechanism of hydrogenation catalyzed by 5 is assumed to be similar to the reaction catalyzed by the analogous catalyst 4 . The detailed mechanism, however, is subject to future study.…”

“…Based on the isoelectronic properties of Fe II and Mn I , we recently prepared a Mn I model of [Fe]-hydrogenase 4 (Figure 1 e), [9] which was active for both H 2 activation and hydrogenation of organic compounds. The Mn I complex was more active and stable than its Fe II analogue.…”

Biomimetic Hydrogenation Catalyzed by a Manganese Model of [Fe]‐Hydrogenase

“…Based on the isoelectronic properties of Fe II and Mn I , we recently prepared a Mn I model of [Fe]‐hydrogenase 4 (Figure e), which was active for both H 2 activation and hydrogenation of organic compounds. The Mn I complex was more active and stable than its Fe II analogue.…”

Crystal Structures of [Fe]-Hydrogenase from Methanolacinia paynteri Suggest a Path of the FeGP-Cofactor Incorporation Process

“…Some of the mimics are composed of similar complex structures to the FeGP cofactor containing Fe(II) [27] or Mn(I) [25] as the metal center with two CO and pyridinol but lack the GMP moiety. Several mimic complexes exhibit catalytic activities of H2 activation and hydride transfer to chemical compounds [22][23][24][25]. Recently, reconstituted active semi-synthetic [Fe]-hydrogenases were produced by incorporation of the mimic The FeGP cofactor is extractable from [Fe]-hydrogenase in the presence of 60% methanol, 1-mM 2-mercaptoethanol and 1% NH 3 [14].…”

“…Many mimic complexes of the FeGP cofactor have been synthesized [2,[21][22][23][24][25][26]. Some of the mimics are composed of similar complex structures to the FeGP cofactor containing Fe(II) [27] or Mn(I) [25] as the metal center with two CO and pyridinol but lack the GMP moiety. Several mimic complexes exhibit catalytic activities of H 2 activation and hydride transfer to chemical compounds [22][23][24][25].…”