Learn More!
(1) Nickel: A Key Cofactor
Ni is an essential trace nutrient for many Bacteria and Archaea and for many plants, but its roles are generally limited to, at most, a handful of enzymes (Ragsdale, 2009; Zhang and Gladyshev, 2010).
​
The single most widely distributed Ni-dependent enzyme, and the only known Ni enzyme in eukaryotes (Zhang et al., 2009), is urease, which plays a key role in N-cycling. Other Ni-dependent proteins include [NiFe] hydrogenase, a Ni form of SOD, and CO dehydrogenase (Kaluarachchi et al., 2010). Ni was relatively abundant in the ancient oceans in which life evolved and anaerobic bacteria and Archaea tend to have the most Ni-dependent enzymes.
​
Many bacteria appear to have only one or two Ni-dependent proteins, but nevertheless have dedicated Ni transport and regulation systems. Other bacteria appear to have dispensed with a Ni requirement.
​
(2) Ni in Methanogenesis
The methanogens are noteworthy for having a relatively large number of Ni-dependent enzymes including some of the key enzymes in methanogenesis itself. The Ni-dependent methyl-CoM reductase is responsible for the production of all biogenic methane and thereby has implications for the global climate both in the Archaean era and as a contributor to global warming today (Singh et al., 2010).
(3) Substituting [NiFe] hydrogenase with [Fe] enzyme
In methanogens, methanogenesis uses a flavin-based cofactor (F420) that is reduced by a hydrogenase. Under Ni-replete conditions, reduction of F420 is catalyzed by a multi-subunit flavoprotein containing both Ni and several Fe/S centers (the [NiFe] hydrogenase). Under Ni-limiting conditions, the specific activity of this enzyme declines at least 100-fold and it is functionally replaced by two other enzymes that do not require Ni and use a tetrahydromethanopterin cofactor. These two enzymes (an [Fe] hydrogenase and an F420-dependent methylenetetrahydromethanopterin dehydrogenase) are upregulated severalfold in response to Ni deficiency (Afting et al., 2000). The [Fe] hydrogenase can functionally replace the [NiFe] enzyme for H2 oxidation, but it is catalytically inferior, so Ni-limited cells must synthesize relatively more [Fe] hydrogenase to maintain the same catalytic efficiency as for the [NiFe] enzyme (Thauer et al., 2010).
​
C. reinhardtii, which also has an active hydrogenase, uses only the [Fe] type of enzyme (Happe et al., 1994), and given its Ni-independent urease, has thereby dispensed with any requirement for Ni as a nutrient.
(4) Substituting Ni-urease with Fe-urease
Helicobacter mustelae is a gastric pathogen of ferrets that is highly reliant on urease, which creates a significant Ni demand. Since ferrets are carnivores, and meat is much lower than vegetable matter in Ni content, H. mustelae may commonly face Ni limitation. The result is the presence of two, differentially-regulated operons encoding urease. When Ni is limiting, and Fe is abundant, expression of the ureA2B2 operon is induced and this Fe-containing urease functionally replaces the Ni-dependent isozyme (Stoof et al., 2008). Although this enzyme is not as active as the Ni isozyme, it is sufficient to provide acid resistance (Carter et al., 2011).
(5) Substituting NiSOD with FeSOD
Despite the relatively low number of Ni-dependent enzymes in most organisms, the presence of alternative, non-Ni- dependent alternatives appears to be common:
​
Streptomyces griseus encodes both a NiSOD and an FeZnSOD. Elevated levels of Ni stimulate the production of NiSOD and repress the FeZnSOD. The latter is due to Ni-dependent metalloregulation that involves a complex of an ArsR-family repressor (SrnR) and a Ni-binding sensor protein (SrnQ) (Kim et al., 2003).
​
A similar reciprocal regulation is observed between NiSOD and FeSOD in Streptomyces coelicolor, but this regulation is mediated by a Ni-sensing Fur family protein designated as Nur. Nur, when bound to Ni, directly represses the transcription of the FeSOD-encoding gene while indirectly activating transcription of the gene for NiSOD (Ahn et al., 2006).
(6) Recycling Ni from Urease to NiSOD
Marine Synechococcus spp. actively transport Ni from their environment and use this metal as a cofactor for both urease and NiSOD. In laboratory studies, the former is required for growth on urea as a nitrogen source, but for one studied ocean isolate (Synechococcus WH8102), Ni is required even when NH4+ is provided as N source (Dupont et al., 2008). This Ni requirement was ascribed to the fact that this organism encodes only a single SOD, which is a Ni enzyme and essential for phototrophic growth. When transferred from urea to NH4+ as nitrogen source, Ni-limited cells were able to grow for several doublings before becoming Ni limited, suggesting that Ni was likely reallocated from urease (which was no longer needed) to NiSOD.