Table of Contents

Arthropod P450 functions

With so many arthropod species, so many P450s and so few researchers in the field, it is no surprise that we know so little about arthropod P450 functions. Even in humans, the function of 3/57 P450s is still unknown and they remain “orphans” with no known substrate (Guengerich, 2022).

In arthropods, such a global, species-wide view is still lacking, with less than half of the P450s of Drosophila melanogaster, Helicoverpa armigera or Apis mellifera being characterized biochemically. Moreover, in humans, of 15 P450s generally thought to be xenobiotic metabolizers, 13 are also acting on endogenous substrates, and of the 38 P450s known to have endogenous substrates, 21 are also capable of metabolizing xenobiotics (Niwa et al., 2009; Durairaj et al, 2019). Documented P450 functions are therefore only a snapshot of the catalytic competence of each P450.

Dermauw et al., 2020 have argued that the dichotomy between roles in physiology or in environmental response is a deceptive one. Several authors have associated single copy genes (from CYP families with single or few genes) with roles in physiology, while multiple paralogs ( from CYP families with many genes or blooms) would be typical of a role in environmental response (e.g. detoxification). However, there are too many examples where such associations are not valid, and increasing observations of shifts between physiology and environmental response that have occurred over evolutionary time. This makes the definition of P450 function particularly difficult. The parable of blind men describing an elephant is appropriate, and the documented functions listed below should be interpreted accordingly.

Documented P450 functions in arthropods

These tables provide surveys by clan and by P450.1)

In vitro activities

Transgenic expression

Null mutants or CRISPR/Cas knockouts

Effects of P450 knockdown by RNAi

A few of these P450s are described in more detail below:

Arthropod conserved physiological functions

* Ecdysteroid metabolism

* CYP15 - Juvenile Hormone biosynthesis

* CYP4G subfamily - cuticular hydrocarbon biosynthesis

Specialized physiological functions

* CYP4C7 - a cockroach terpenoid ω-hydroxylase

* CYP9T2-3 - Ips pini bark beetle pheromone biosynthesis

* CYP6CR1 - Dendroctonus bark beetle pheromone biosynthesis

* CYP6DE1 - bark beetle aggregation pheromone biosynthesis

* Cyanogenic glucoside biosynthesis

* lepidopteran alkenyl sex pheromones

* house fly sex pheromone biosynthesis

* honey bee mandibular gland pheromones

* stink bug aggregation / sex pheromones

Xenobiotic metabolism

* CYP6A1 from the housefly

* paralogous CYP6AE from Helicoverpa armigera

* orthologous CYP9Q in bees

1)
Updated and expanded summaries of data presented in Feyereisen (2012), Vontas et al. (2020) and Katsavou et al. (2021).