Recent advances in utilization of ferredoxins for biosynthesis of valuable compounds

Ferredoxin (Fd) is a small metalloprotein holding one or two Fe-S clusters in its inner shell. Like many other metalloproteins, Fd is redox active and involved in electron transfer during cellular metabolism. The electrons from reduced Fd are mostly used to regenerate NADPH under physiological conditions. Increasing number of attempts have been reported, however, where Fd delivers electrons to enable biosynthesis of valuable compounds. Various compounds ranging from H₂ to vitamin D₃ have been synthesized successfully using electrons mediated by Fd molecules. In this review, we provide an overview of the engineering studies utilizing Fd for biosynthesis of targeted molecules. The emphasis is on the role and activity of Fd as well as the methods used to improve the rate of electron transfer. Both microbial and electrochemical biosynthesis technologies are described and compared with respect to productivity and the compound being produced. In addition to the ferredoxins from the microbial organisms, artificially designed de novo types are described, highlighting the potential of the emerging computational methods used in metabolic and protein engineering. We believe that the recent advances in utilization of Fd for biosynthesis can result in breakthrough innovation across the biotechnology industry.