title: Production of 3-Oxo-2-(2'-pentenyl)-cyclopentane-1-octanoic Acid in the Fungus Aspergillus oryzae: A Step Towards Heterologous Production of Pyrethrins in Fungi.
abstract: Pyrethrins are natural insecticides, which accumulate to high concentrations in pyrethrum (Chrysanthemum cinerariaefolium) flowers. Synthetic pyrethroids are more stable, more efficacious and cheaper, but contemporary requirements for safe and environmentally friendly pesticides encourage a return to the use of natural pyrethrins, and this would be favoured by development of an efficient route to their production by microbial fermentation. The biosynthesis of pyrethrins involves ester linkage between an acid moiety (chrysanthemoyl or pyrethroyl, synthesised via the mevalonic acid pathway from glucose), and an alcohol (pyrethrolone). Pyrethrolone is generated from 3-oxo-2-(2'-pentenyl)-cyclopentane-1-octanoic acid, which originates from α-linolenic acid via the jasmonic acid biosynthetic cascade. The first four genes in this cascade, encoding lipoxygenase 2, allene-oxide synthase, allene-oxide cyclase 2 and 12-oxophytodienoic acid reductase 3, were amplified from an Arabidopsis thaliana cDNA library, cloned in a purpose-built fungal multigene expression vector and expressed in Aspergillus oryzae. HPLC-MS analysis of the transgenic fungus homogenate gave good evidence for the presence of 3-oxo-2-(2'-pentenyl)-cyclopentane-1-octanoic acid.
authors.affiliation: School of Biological Sciences, University of Bristol, Life Sciences Building, 24 Tyndall Avenue, Bristol, BS8 1TQ, UK. memohamed@kfu.edu.sa.|Department of Pharmacognosy, College of Pharmacy, University of Zagazig, Zagazig, 44519, Egypt. memohamed@kfu.edu.sa.|Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, P.O. 380, Ahsaa, 31982, Kingdom of Saudi Arabia. memohamed@kfu.edu.sa.
authors.forename: Maged E
authors.initials: ME
authors.lastname: Mohamed
authors.affiliation: School of Biological Sciences, University of Bristol, Life Sciences Building, 24 Tyndall Avenue, Bristol, BS8 1TQ, UK.|Faculty of Agro-Based Industry, Universiti Malaysia Kelantan, Locked Bag No. 100, 17600, Jeli, Kelantan, Malaysia.
authors.forename: Khomaizon A K
authors.initials: KA
authors.lastname: Pahirulzaman
authors.affiliation: School of Biological Sciences, University of Bristol, Life Sciences Building, 24 Tyndall Avenue, Bristol, BS8 1TQ, UK.
authors.forename: Colin M
authors.initials: CM
authors.lastname: Lazarus
mesh_terms: D017360:Arabidopsis / Q000201:enzymology* / Q000235:genetics; D029681:Arabidopsis Proteins / Q000235:genetics* / Q000378:metabolism; D001236:Aspergillus oryzae / Q000235:genetics* / Q000378:metabolism; D057005:Bioengineering; D053898:Biosynthetic Pathways; D002210:Caprylates / Q000378:metabolism*; D005285:Fermentation; D015723:Gene Library; D007306:Insecticides / Q000378:metabolism; D011722:Pyrethrins / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C092226:ATLP-1 protein, Arabidopsis; D029681:Arabidopsis Proteins; D002210:Caprylates; D007306:Insecticides; D011722:Pyrethrins; D011994:Recombinant Proteins; C003255:pyrethrosin
keywords: 3-Oxo-2-(2′-pentenyl)-cyclopentane-1-octanoic acid; Aspergillus oryzae; Biosynthesis; Heterologous gene expression; Pyrethrins