1. Research Progress relating to the role of cytochrome P450 in the biosynthesis of terpenoids in medicinal plants Yu-Jun Zhao.Qi-Qing.Ping Su.Xin Chen.Xiu-juan.Wei.Lu-Qi By judy mutua

2. Introduction Terpenoids are plant natural products with isoprene as their structural unit.

3. Terpenoid Biosynthesis

5. Cytotochrome P450 Hemoproteins-The active site of cytochrome P450 contains a heme-iron center.

6. CYP450 Spectrum The term P450 is derived from the spectrophotometric peak at the wavelength of the absorption maximum of the enzyme (450 nm) when it is in the reduced state and complexed with CO

7. Different cytochrome P450 systems Most CYPs require a protein partner to deliver one or more electrons.

8. Examples of plant cytochromes P450 FunctionPlant Species CYP93E2β-Balsams alcohol-11- hydroxylase Barrel Clover (Medicago truncatula) CYP71AV1Amorpha-4,11-diene C-12 oxidase Artemesia annua CYP76B6Geraniol 10- hydroxylase Madagascar periwinkle (Catharanthus roseus) CYP725A- like Taxadiene 5-α- hydroxylase Japanese Yew (Taxus cuspidata) CYP88D6Β-Amyrin 11-oxidaseChinese liquorice (Glycyrrhiza uralensis)

9. The main active Ingredient is glycyrrhizic acid used to treat cancer & AIDS.

10. Biosynthesis of Glycyrrhizin.

11. Identification of Licorice β-amyrin 11-oxidase CYP72 CYP83 CYP88 CYP714 ↘ ↓ ↓ ↙ Conversion of β-amyrin Transfected insect cells

12. Identification of Licorice β-amyrin 11-oxidase

13. Challenges in Terpenoid synthesis Low abundance in their host organism. low yields. high consumption of natural resources. Chemical synthesis difficult to scale for industrial production.

14. Comparison of hosts CharacteristicBacterial cellsPlant cells Size1µm20-50µm Shear stressInsensitiveSensitive Doubling Time< 1 hourDays Batch Fermentation time DaysWeeks Product YieldsHighlow Precursorspoorrich Native conditionsnoyes CYP450 enzymesAbsentpresent

15. Conclusion Traditional engineering strategies result to unbalanced carbon flux and accumulation of toxic intermediates that inhibit growth. The utilisation of genetic engineering to regulate gene expression and obtain large quantities of terpene compounds should be explored fully.