Cytochrome P450 debuted to the world of science in 1958 as an unusual spectrum
taken from rat liver microsomes with a peak of absorbance at 450 nm [1].
Fifty four years later, we know more than 18 500 examples of the P450 molecule
from hundreds of species [2]. The level of detail for these proteins varies
from multiple crystal structures (over 80 for cytochrome P450cam) with simulated
movies of their active sites to just a fragment from a transcriptome
project. Inbetween, we have glimpsed the importance of P450 for biology,
and it has been applied for human benefit in the pharmaceutical industry,
agriculture, biotechnology and even aesthetics.
This special issue ‘Cytochrome P450 and its impact on planet Earth’ poses
the question: how would the Earth be different without cytochrome P450s?
The eukaryotic cell, with its larger size and greater energy capacity due to mitochondrial
function, exposed a gateway for multicellularity that has not been
exploited by archaea or bacteria except for a few myxobacteria and filamentous
branching cyanobacteria [3]. An essential transition to the eukaryotic cell was a
change in the cell membrane to allow phagocytosis. The membrane alteration
called by Cavalier-Smith the neomuran revolution was linked to the presence
of cholesterol in the membranes, a eukaryotic hallmark [4]. The ability to
make sterols depends directly on the P450 CYP51, so in some degree or fashion
the Earth would probably not contain significant multicellular life without
CYP51 impacting the composition and properties of membranes at the dawn
of eukaryotes.
Moving forward in time from multicellularity to the conquest of the land,
we find P450’s contributions essential in many ways. In leaving the water,
plants needed a waterproof coating so that they would not dehydrate. Pathways
evolved for making the cutins and suberins used in forming epicuticular waxes.
Fatty acid and alkane hydroxylases in the CYP86 clan provided this function,
without which the land would be surrounded by an algal pond scum and
little more. A similar hydrophobic coating covers insects, or they die at hatching.
This coating is provided by CYP4G1 in Drosophila and its orthologues in
other species [5]. These hydrocarbons are the target of P450s of the entomopathogenic
fungus Beauveria bassiana as described in the article by Kelly &
Kelly [6].
If a cuticle is assumed for existence on dry land, what other key aspects of
life on land are P450 dependent? Lignin is the support molecule for woody
plants. The tallest plants without lignin are mosses [7]. Lignin is a product of
P450 reactions in the phenylpropanoid and monolignol pathways (CYP73,
CYP98 and CYP84). It is used for making tracheids and vessels for water conduction
and it offers support for upward growth. The famous dictum ‘Allest ist
Blat’ (all is leaf ) by Goethe [8] would not be true for there would be no leaves as