Anaerobic Radical Enzymes for Biotechnology

Abstract

Enzymes that proceed through radical intermediates have a rich chemistry that includes functionalization of otherwise unreactive carbon atoms, carbonskeleton rearrangements, aromatic reductions, and unusual eliminations. Especially under anaerobic conditions, organisms have developed a wide range of approaches for managing these transformations that can be exploited to generate new biological routes towards both bulk and specialty chemicals. These routes are often either much more direct or allow access to molecules that are inaccessible through standard (bio)chemical approaches. This review gives an overview of some of the key enzymes in this area: benzoyl-CoA reductases effecting the enzymatic Birch reduction, ketyl radical dehydratases, coenzyme B 12 -dependent enzymes, glycyl radical enzymes, and radical SAM (AdoMet radical) enzymes. These enzymes are discussed alongside biotechnological applications, highlighting the wide range of actual and potential uses. With the increased diversity in biotechnological approaches to obtaining these enzymes and information about them, even more of these enzymes can be expected to find application in industrial processes.

Ground-State Electron Transfer as an Initiation Mechanism for Asymmetric Hydroalkylations in Radical Biocatalysis

“…[5][6][7] Nature has evolved various biocatalysts, such as cobalamin and radical S-adenosylmethionine (SAM) enzymes, to catalyze the radical-mediated transformations with unparalleled chemo-, regio-, and enantioselectivity in the biosynthesis of complex natural products. [8][9][10][11][12] However, these enzymes are not readily harnessed outside of their natural settings by organic synthetic chemists, owing to either operational difficulties or lack of catalytic versatility. We imagined that enzymes could be used more broadly to solve selectivity challenges in the radical literature by identifying and developing enzymes that can use non-natural mechanisms for radical formation.…”

Radical Stabilization Energies for Enzyme Engineering: Tackling the Substrate Scope of the Radical Enzyme QueE

“…As such, it would be highly beneficial to gain access to and adapt these biotransformations for their use in industrial biotechnological applications, facilitating sustainable routes towards fine chemicals, pharmaceuticals, or bulk chemicals that would be highly challenging to synthesize by alternative methods. 3 The key commonality for the catalysis of radical SAM enzymes is that they use S-adenosylmethione (SAM) either as cofactor or co-substrate. SAM is bound to a central Fe 4 S 4 iron sulfur cluster responsible for initiating the redox reaction.…”

The Influence of Chemical Change on Protein Dynamics: A Case Study with Pyruvate Formate‐Lyase

“…This process is catalyzed by the PFL activating enzyme (PFL‐AE), which is a member of the radical S ‐adenosylmethionine (SAM) enzyme superfamily . Such radical enzymes are receiving increased interest because of their potential applications in biotechnology and biochemical engineering, and most recently also in the context of enzyme engineering …”