Cluster assembly in nitrogenase.

The versatile enzyme system nitrogenase accomplishes the challenging reduction of Nand other substrates through the use of two main metalloclusters. For molybdenum nitrogenase, the catalytic component NifDK contains the [FeS]-core P-cluster and a [MoFeSC-homocitrate] cofactor called the M-cluster. These chemically unprecedented metalloclusters play a critical role in the reduction of N, and both originate from [FeS] clusters produced by the actions of NifS and NifU. Maturation of P-cluster begins with a pair of these [FeS] clusters on NifDK called the P*-cluster. An accessory protein NifZ aids in P-cluster fusion, and reductive coupling is facilitated by NifH in a stepwise manner to form P-cluster on each half of NifDK. For M-cluster biosynthesis, two [FeS] clusters on NifB are coupled with a carbon atom in a radical-SAM dependent process, and concomitant addition of a 'ninth' sulfur atom generates the [FeSC]-core L-cluster. On the scaffold protein NifEN, L-cluster is matured to M-cluster by the addition of Mo and homocitrate provided by NifH. Finally, matured M-cluster in NifEN is directly transferred to NifDK, where a conformational change locks the cofactor in place. Mechanistic insights into these fascinating biosynthetic processes are detailed in this chapter.

© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.