Directed evolution of squalene synthase for dehydrosqualene biosynthesis
نویسندگان
چکیده
منابع مشابه
Dual dehydrosqualene/squalene synthase inhibitors: leads for innate immune system-based therapeutics.
With the rapid rise in bacterial drug resistance, there is great interest in developing innovative approaches to anti-infective therapy. For example, in the United States, more people die from Staphylococcus aureus infections than die from human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Alternative approaches are thus of interest, and as discussed in a recent Natio...
متن کاملPhosphonosulfonates are potent, selective inhibitors of dehydrosqualene synthase and staphyloxanthin biosynthesis in Staphylococcus aureus.
Staphylococcus aureus produces a golden carotenoid virulence factor called staphyloxanthin (STX), and we report here the inhibition of the enzyme, dehydrosqualene synthase (CrtM), responsible for the first committed step in STX biosynthesis. The most active compounds are halogen-substituted phosphonosulfonates, with K(i) values as low as 5 nM against the enzyme and IC(50) values for STX inhibit...
متن کاملBisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis.
Some bisphosphonates used for the treatment of bone disorders are also potent inhibitors of squalene synthase, a critical enzyme for sterol biosynthesis. Among seven drugs tested, YM 175 (cycloheptylaminomethylene-1,1-bisphosphonic acid) was the most potent inhibitor of rat liver microsomal squalene synthase (Ki = 57 nM) and sterol biosynthesis from [14C]mevalonate in rat liver homogenate (IC50...
متن کاملMechanism of action and inhibition of dehydrosqualene synthase.
"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. Here, we report the structures of Staphylococcus aureus dehydrosqualene synthase (CrtM) complexed with its reaction intermediate, presqualene diphosphate (PSPP), the dehydros...
متن کاملRegulation of squalene synthase, a key enzyme of sterol biosynthesis, in tobacco.
Squalene synthase (SS) represents a putative branch point in the isoprenoid biosynthetic pathway capable of diverting carbon flow specifically to the biosynthesis of sterols and, hence, is considered a potential regulatory point for sterol metabolism. For example, when plant cells grown in suspension culture are challenged with fungal elicitors, suppression of sterol biosynthesis has been corre...
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ژورنال
عنوان ژورنال: FEBS Letters
سال: 2014
ISSN: 0014-5793
DOI: 10.1016/j.febslet.2014.07.028