title: Characterization of a feedback-resistant mevalonate kinase from the archaeon Methanosarcina mazei.
abstract: The mevalonate pathway is utilized for the biosynthesis of isoprenoids in many bacterial, eukaryotic, and archaeal organisms. Based on previous reports of its feedback inhibition, mevalonate kinase (MVK) may play an important regulatory role in the biosynthesis of mevalonate pathway-derived compounds. Here we report the purification, kinetic characterization, and inhibition analysis of the MVK from the archaeon Methanosarcina mazei. The inhibition of the M. mazei MVK by the following metabolites derived from the mevalonate pathway was explored: dimethylallyl diphosphate (DMAPP), geranyl pyrophosphate (GPP), farnesyl pyrophosphate (FPP), isopentenyl monophosphate (IP), and diphosphomevalonate. M. mazei MVK was not inhibited by DMAPP, GPP, FPP, diphosphomevalonate, or IP, a proposed intermediate in an alternative isoprenoid pathway present in archaea. Our findings suggest that the M. mazei MVK represents a distinct class of mevalonate kinases that can be differentiated from previously characterized MVKs based on its inhibition profile.
authors: Genencor, 925 Page Mill Road, Palo Alto, CA 94304, USA.
authors: Yuliya A
authors: YA
authors: Primak
authors: Mai
authors: M
authors: Du
authors: Michael C
authors: MC
authors: Miller
authors: Derek H
authors: DH
authors: Wells
authors: Alex T
authors: AT
authors: Nielsen
authors: Walter
authors: W
authors: Weyler
authors: Zachary Q
authors: ZQ
authors: Beck
mesh_terms: D019843:Archaeal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D053898:Biosynthetic Pathways; D016000:Cluster Analysis; D025461:Feedback, Physiological; D007700:Kinetics; D017020:Methanosarcina / Q000201:enzymology* / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D013729:Terpenes / Q000378:metabolism*
chemical_list: D019843:Archaeal Proteins; D013729:Terpenes; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase