Arthropod P450 Dokuwiki

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===== CYP4C7 - a cockroach terpenoid ω-hydroxylase - =====
 

In corpora allata of the cockroach, //Diploptera punctata//, expression of the [[CYP15|CYP15A1]] gene is high when JH synthetic levels are high (Helvig et al., 2004). Another P450 gene, CYP4C7, is also selectively expressed in the corpora allata (CA)(Sutherland et al., 1998). It has an expression pattern that //mirrors// the pattern of JH synthesis. The recombinant CYP4C7 enzyme produced in //E. coli// metabolizes a variety of sesquiterpenoids but not mono- or diterpenes. In addition to metabolizing JH precursors, farnesol, farnesal, farnesoic acid and methyl farnesoate, it also metabolizes JH III to a major metabolite identified as (10E)-12-hydroxy-JH III (Sutherland et al., 1998). {{ ::4c7activity.jpg?400|substrate selectivity of CYP4C7}}

Although this ω-hydroxylated JH III has not been identified as a product of the CA, //Locusta migratoria// CA are known to produce several hydroxylated JHs in the radiochemical assay in vitro (Darrouzet et al., 1997; Mauchamp et al., 1999). These hydroxy-JHs, 8'-OH-, 12'-OH (Darrouzet et al., 1997) and 4'-OH-JH III (Mauchamp et al., 1999) may be major products of the CA after JH III itself and their role is unknown. Their presence suggests that locust CA have a P450 functionally homologous to cockroach CYP4C7 that has a lower regioselectivity (or that there are more than one P450 of this kind). Indeed, the hydroxy-JHs can be synthesized by locust CA from JH III, and this hydroxylation is inhibited by CO and piperonyl butoxide (Couillaud et al., 1996).

The tight physiological regulation of CYP4C7 expression in adult female //Diploptera punctata// (Sutherland et al., 2000) indicates that the terpenoid ω-hydroxylase has an important function to play at the end of vitellogenesis and at the time of impending chorionation and ovulation. It was hypothesized (Sutherland et al., 1998, Sutherland et al., 2000) that this hydroxylation was a first step in the inactivation of the very large amounts of JH and JH precursors present in the CA of this species after the peak of JH synthesis. Indeed, topical treatment with JH III after the peak of JH synthesis on day 5 caused an inhibition of ovulation and abortion of ovulated eggs. 

{{ ::cyp4c7-jh.jpg?300 |}}
Changes in CYP4C7 mRNA levels in the corpora allata during a gonotrophic cycle in mated female //Diploptera punctata// (open squares) and changes in synthetic activity of the glands (filled dots). From Sutherland et al. 2000. 
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%%>%%Diploptera_punctata-CYP4C7-AAC69184
AVLLLTSLAIVVVYLCRRLNFWVKLRSVPGPPALPFLGNSLILRGTQEEFFRLLSKCATKYGNIFRLWVG
QRPFVFLYSAEAIQPILNSTVYIDKSYEYSFLFPWLGTGLLTSTGNKWHTRRKLLTQSFHSKVLEDFLEP
IYQHSLFLCNRLELELDKPHFKVTPYAKLCALDIICDTAMGSTINAQENSQSEYVTAVDSLSEIVQRRFI
TPWLKPDFLFKMTKLGKKQEQCLKIVHNFTRKVINERKEDKLRQNNLEVEISQQNGIKKKHRLALLDLLL
ELSENGKVLTDEDICEEVDTFMFAGHDTIASGVSWILYVLGHHLDSQEKIVEEFKNVMEEDNTEWPTMKH
LNKLCYLERCIKEAMRLYPVVPLIARNLTQPIKIMDYMLPEGVTILINTYLLHRDSRFFPNPDIFEPDRF
LTSNCEARNPFAYVPFSAGPRNCIGQKFAMMELKIILSTVLQRFIVKSVDKEERLKLVGELVLLNRDGIR
LTITART
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Couillaud, F., Debernard, S., Darrouzet, E., and Rossignol, F. 1996. Hidden face of juvenile hormone metabolism in the African locust. //Arch Insect Biochem Physiol// 32, 387-397.

Darrouzet, E., Mauchamp, B., Prestwich, G. D., Kerhoas, L., Ujvary, I., and Couillaud, F. 1997. Hydroxy juvenile hormones: new putative juvenile hormones biosynthesized by locust corpora allata in vitro. //Biochem Biophys Res Commun// 240, 752-8.

Helvig C, Koener J, Unnithan G, Feyereisen R. 2004. CYP15A1, the cytochrome P450 that catalyzes epoxidation of methyl farnesoate to Juvenile Hormone III in cockroach corpora allata. //Proc Natl Acad Sci U S A// 101: 4024-4029.

Mauchamp, B., Darrouzet, E., Malosse, C., and  Couillaud, F. 1999. 4'-OH-JH-III: an additional hydroxylated juvenile hormone produced by locust corpora allata in vitro. //Insect Biochemistry and Molecular Biology// 29, 475-480.


Sutherland, T., Unnithan, G., Andersen, J., Evans, P., Murataliev, M., Szabo, L., Mash, E., Bowers, W., Feyereisen, R. 1998. A cytochrome P450 terpenoid hydroxylase linked to the suppression of insect juvenile hormone synthesis. //Proc Natl Acad Sci U S A// 95, 12884-12889.

Sutherland, T., Unnithan, G., Feyereisen, R. 2000. Terpenoid omega-hydroxylase (CYP4C7) messenger RNA levels in the corpora allata: a marker for ovarian control of juvenile hormone synthesis in //Diploptera punctata//. //J Insect Physiol// 46, 1219-1227.