Figure 1, Key Figure. A schematic overview of various ferredoxin (ptFd) and ferredoxin-NADP⁺ reductase (ptFNR)-dependent metabolic pathways in the apicoplast.

ptFd reduction is catalyzed by NADPH-dependent enzyme ptFNR and could donate electrons (e⁻) to four other FeS- proteins, and probably to early steps of FeS synthesis itself. The NADP transhydrogenase (NTH) is suggested to provide NADPH for ptFd reduction by ptFNR. The SUF FeS synthesis pathway uses a cysteine desulfurase to mobilize sulfur from the available cysteine pool and transfer it to the scaffold protein complex with the aid of a relay protein. FeS cofactors formed on the scaffold complex are transferred to target proteins (light red) by the carrier proteins. Two proteins, IspG and IspH, that receive electrons from ptFd are the last two enzymes of the essential MEP pathway. The glycolytic metabolites pyruvate (Pyr) and glyceraldehyde-3 phosphate (GA3P) are substrates for the MEP pathway and thought to be imported by apicoplast transporters. In seven subsequent enzymatic reactions the substrates are converted into IPP and DMAPP. DXPR is the target of Fosmidomycin (Fos). Other ptFd/FNR-dependent proteins are LipA (lipoate synthase) of the lipoate synthesis pathway and MiaB (tRNA-i⁶A37 methylthiotransferase) responsible for ms²i⁶A (2-methylthiol-N⁶-isopentenyl adenosine) tRNA modification. DOXP, 1-deoxy-D-xylulose 5-phosphate; DXPR, DOXP-reductoisomerase; IspD, 2C-Methyl-D-erythritol 4-Phosphate Cytidyltransferase; IspE, 4-diphosphocytidyl-2C-methyl-D-erythritol kinase; IspF, 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase; IspG, hydroxylmethylbutenyl diphosphate (HMBPP) synthase; IspH, HMBPP reductase; DMAPP, dimethylallyl pyrophosphate; IPP, isopentenyl pyrophosphate; Cys, cysteine; Ala, alanine; Fe, iron; i⁶A, N⁶-isopentenyl adenosine; MiaA, tRNA isopentenyltransferase; ms²i⁶A, 2-methylthiol-N⁶-isopentenyl adenosine; C8:ACP, octanoyl acyl carrier protein; FASII, type II fatty acid synthesis pathway; LipB, lipoate (octanoyl)transferase; PDH, pyruvate dehydrogenase; Ac-CoA, acetyl CoA. Figure created with BioRender.com.