SCAN:Desulfovibrio helps unlock an alternative heme biosynthetic pathway

ITQB-Scan Seminar

Title: Desulfovibrio helps unlock an alternative heme biosynthetic pathway

Speaker: Susana Lobo

From: Molecular Genetics of Microbial Resistance Laboratory

Abstract:

Desulfovibrio spp are sulfate-reducing bacteria of ecological and biotechnological importance. In spite of containing a large number of essential proteins with metal-modified tetrapyrroles cofactors, the biosynthetic pathway of these tetrapyrroles is poorly understood. Our laboratory has been addressing the study of biosynthesis of the tetrapyrrole framework using the Desulfovibrio model organism D. vulgaris Hildenborough, for which the genome is available. To this end, we performed the biochemical characterization of the several gene products putatively involved in the steps from aminolevulinic acid to sirohydrochlorin and cobalt-sirohydrochlorin. We observed that, contrary to what is usually seen, uroporphyrinogen III synthase and uroporphyrinogen III methyltransferase genes are fused forming a bifunctional protein (HemD-CobA). Additionally, D. vulgaris contains two distinct sirohydrochlorin cobaltochelatases, the cytoplasmic CbiKC and the periplasmic heme containing CbiKP with unique structural features. The tridimensional structure of CbiKP showed how the heme is binding to the enzyme. Comparison of its structure  with other known chelatases allow inferring the evolution of the form and function of microbial chelatases.
Importantly, we have very recently shown that Desulfovibrio synthesize heme through an alternative and, so far, novel pathway, which involves reactions catalyzed by previously uncharacterized enzymes that convert the siroheme intermediary into heme prosthetic group.