Although members of this family are highly similar to HemN, they lack the catalytic residues to perform the HemN reaction, thus are NOT oxygen-indpendent coproporphyrinogen III oxidases.
Goto T, Aoki R, Minamizaki K, Fujita Y
Functional differentiation of two analogous coproporphyrinogen III oxidases for heme and chlorophyll biosynthesis pathways in the cyanobacterium Synechocystis sp. PCC 6803
▸ Abstract
Coproporphyrinogen III oxidase (CPO) catalyzes the oxidative decarboxylation of coproporphyrinogen III to form protoporphyrinogen IX in heme biosynthesis and is shared in chlorophyll biosynthesis in photosynthetic organisms. There are two analogous CPOs, oxygen-dependent (HemF) and oxygen-independent (HemN) CPOs, in various organisms. Little information on cyanobacterial CPOs has been available to date. In the genome of the cyanobacterium Synechocystis sp. PCC 6803 there is one hemF-like gene, sll1185, and two hemN-like genes, sll1876 and sll1917. The three genes were overexpressed in Escherichia coli and purified to homogeneity. Sll1185 showed CPO activity under both aerobic and anaerobic conditions. While Sll1876 and Sll1917 showed absorbance spectra indicative of Fe-S proteins, only Sll1876 showed CPO activity under anaerobic conditions. Three mutants lacking one of these genes were isolated. The Deltasll1185 mutant failed to grow under aerobic conditions, with accumulation of coproporphyrin III. This growth defect was restored by cultivation under micro-oxic conditions. The growth of the Deltasll1876 mutant was significantly slower than that of the wild type under micro-oxic conditions, while it grew normally under aerobic conditions. Coproporphyrin III was accumulated at a low but significant level in the Deltasll1876 mutant grown under micro-oxic conditions. There was no detectable phenotype in Deltasll1917 under the conditions we examined. These results suggested that sll1185 encodes HemF as the sole CPO under aerobic conditions and that sll1876 encodes HemN operating under micro-oxic conditions, together with HemF. Such a differential operation of CPOs would ensure the stable supply of tetrapyrrole pigments under environments where oxygen levels fluctuate greatly.
Dailey HA, Gerdes S, Dailey TA, Burch JS, Phillips JD
Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin
▸ Abstract
It has been generally accepted that biosynthesis of protoheme (heme) uses a common set of core metabolic intermediates that includes protoporphyrin. Herein, we show that the Actinobacteria and Firmicutes (high-GC and low-GC Gram-positive bacteria) are unable to synthesize protoporphyrin. Instead, they oxidize coproporphyrinogen to coproporphyrin, insert ferrous iron to make Fe-coproporphyrin (coproheme), and then decarboxylate coproheme to generate protoheme. This pathway is specified by three genes named hemY, hemH, and hemQ. The analysis of 982 representative prokaryotic genomes is consistent with this pathway being the most ancient heme synthesis pathway in the Eubacteria. Our results identifying a previously unknown branch of tetrapyrrole synthesis support a significant shift from current models for the evolution of bacterial heme and chlorophyll synthesis. Because some organisms that possess this coproporphyrin-dependent branch are major causes of human disease, HemQ is a novel pharmacological target of significant therapeutic relevance, particularly given high rates of antimicrobial resistance among these pathogens.
Proc Natl Acad Sci U S A
2015;112(7):2210-2215
| PubMed ID:
25646457
Radical SAM family enzyme, similar to coproporphyrinogen III oxidase, oxygen-independent, clustered with nucleoside-triphosphatase RdgB (Class C in the Dailey PNAS paper)
