Disulfide bond formation in prokaryotes


Interest in protein disulfide bond formation has recently increased because of the prominent role of disulfide bonds in bacterial virulence and survival. The first discovered pathway that introduces disulfide bonds into cell envelope proteins consists of Escherichia coli enzymes DsbA and DsbB. Since its discovery, variations on the DsbAB pathway have been found in bacteria and archaea, probably reflecting specific requirements for survival in their ecological niches. One variation found amongst Actinobacteria and Cyanobacteria is the replacement of DsbB by a homologue of human vitamin K epoxide reductase. Many Gram-positive bacteria express enzymes involved in disulfide bond formation that are similar, but non-homologous, to DsbAB. While bacterial pathways promote disulfide bond formation in the bacterial cell envelope, some archaeal extremophiles express proteins with disulfide bonds both in the cytoplasm and in the extra-cytoplasmic space, possibly to stabilize proteins in the face of extreme conditions, such as growth at high temperatures. Here, we summarize the diversity of disulfide-bond-catalysing systems across prokaryotic lineages, discuss examples for understanding the biological basis of such systems, and present perspectives on how such systems are enabling advances in biomedical engineering and drug development.

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Fig. 1: A ‘Tree of Life’ diagram showing the DsbAB, DsbA–VKOR and non-disulfide clades.
Fig. 2: DsbAB pathways mediating disulfide bond formation.
Fig. 3: DSB formation in Gram-positive bacteria.
Fig. 4: Cytoplasmic disulfide formation in Archaea.


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This work was supported by US National Institute of General Medical Sciences grants GMO41883 (to J.B. and D.B.) and by an industry research agreement with F. Hoffmann-La Roche Ltd. and F. Hoffmann-La Roche Inc. (to J.B. and D.B.). J.B. is an American Cancer Society Professor.

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C.L. and J.B. wrote the manuscript. D.B. performed the bioinformatic analysis.

Correspondence to Jon Beckwith.

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Landeta, C., Boyd, D. & Beckwith, J. Disulfide bond formation in prokaryotes. Nat Microbiol 3, 270–280 (2018). https://doi.org/10.1038/s41564-017-0106-2

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