Head-to-head terpene synthases: Mechanism of action and inhibition
type: CreativeWork
description: “Head-to-head” terpene synthases catalyze the first committed steps in sterol and carotenoid biosynthesis: the condensation of two isoprenoid diphosphates to form cyclopropylcarbinyl diphosphates, followed by ring opening. In this work, I used x-ray crystallography, and mutagenesis to study the catalytic mechanism of Staphylococcus aureus dehydrosqualene synthase. Dehydrosqualene synthase (CrtM) is also the first committed enzyme in the biosynthesis of staphyloxanthin, a carotenoid pigment, and a major virulence factor in S. aureus. Inhibitors targeting CrtM and staphyloxanthin biosynthesis are therefore of interest as “anti-virulence” based therapy for treating S. aureus infection. I studied the structure-activity-relationship of phosphonosulfonate and phosphonoacetamide compounds in CrtM inhibition, and I also developed a series of non-phosphonate CrtM inhibitors using rational- and structure-based approaches.
abstract: “Head-to-head” terpene synthases catalyze the first committed steps in sterol and carotenoid biosynthesis: the condensation of two isoprenoid diphosphates to form cyclopropylcarbinyl diphosphates, followed by ring opening. In this work, I used x-ray crystallography, and mutagenesis to study the catalytic mechanism of Staphylococcus aureus dehydrosqualene synthase. Dehydrosqualene synthase (CrtM) is also the first committed enzyme in the biosynthesis of staphyloxanthin, a carotenoid pigment, and a major virulence factor in S. aureus. Inhibitors targeting CrtM and staphyloxanthin biosynthesis are therefore of interest as “anti-virulence” based therapy for treating S. aureus infection. I studied the structure-activity-relationship of phosphonosulfonate and phosphonoacetamide compounds in CrtM inhibition, and I also developed a series of non-phosphonate CrtM inhibitors using rational- and structure-based approaches.
author: Lin, Fu-Yang
language: en
keywords: terpenes, isoprenoids, antibiotics, virulence factor, dehydrosqualene synthase, Dehydrosqualene synthase (CrtM), squalene synthase (SQS), drug design, high throughput screening
date published: 2011-05-25T14:27:33Z
date modified: 2026-07-22T22:25:23Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/24489