Regulation of bacterial haem biosynthesis

Haem b and sirohaem are two iron-chelated modified tetrapyrroles that serve as prosthetic groups in proteins with crucial roles in a variety of biological functions, such as gas transport, respiration, and nitrite and sulphite reduction. These tetrapyrroles are synthesised from 5-aminolaevulinic acid and share a common pathway until the formation of uroporphyrinogen III, from where the synthesis diverges. In bacteria, sirohaem is produced from uroporphyrinogen III through the activities of one, two or three separate proteins, while haem b is synthesised through three distinct pathways. The biosynthesis of haem b and sirohaem comprises intermediates and end-products that are unstable or potentially hazardous to the cell. Therefore, the cellular metabolic fluxes of tetrapyrroles need to be tightly controlled by substrate channelling and/or other regulatory processes. This review summarises the recent advances on the regulation and protein–protein interactions controlling the formation of sirohaem and haem b in bacteria.