RRC ID 77211
Author Abe T, Hakamata M, Nishiyama A, Tateishi Y, Matsumoto S, Hemmi H, Ueda D, Sato T.
Title Identification and functional analysis of a new type of Z,E-mixed prenyl reductase from mycobacteria.
Journal FEBS J
Abstract Isoprenoids with reduced Z,E-mixed prenyl groups are found in various organisms. To date, only polyprenol reductases (PR-Dol) involved in dolichol biosynthesis have been identified as enzymes capable of reducing Z,E-mixed prenyl groups. Although C35 -isoprenoids with reduced Z,E-mixed prenyl groups are found in mycobacteria, Z,E-mixed heptaprenyl reductase (HepR) remains unidentified. In the present study, the identification and functional analysis of HepR was performed. No PR-Dol homolog gene was detected in the genome of Mycolicibacterium vanbaalenii. However, a homolog of geranylgeranyl reductase (GGR), which reacts with an all-E prenyl group as a substrate, was encoded in the genome; thus, we analyzed it as a HepR candidate. In vitro enzymatic assay and in vivo gene suppression analysis identified the GGR homolog as HepR and revealed that HepR catalyzes the reduction of ω- and E- prenyl units in Z,E-mixed heptaprenyl diphosphates, and C35 -isoprenoids are mainly biosynthesized using E,E,E-geranylgeranyl diphosphate as a precursor. Thus, it was demonstrated that the Z,E-mixed prenyl reductase family exists in the GGR homologs. To the best of our knowledge, this is the first identification of a new type of Z,E-mixed prenyl reductase with no sequence homology to PR-Dol. The substrate specificity of HepR significantly differed from that of GGR, suggesting that it is a new enzyme. HepR homologs are widely distributed in mycobacterial genomes, and lipid analysis suggests that many strains, including pathogenic species, produce HepR metabolites. The discovery of this new enzyme will promote further research on Z,E-mixed isoprenoids.
Volume 289(16)
Pages 4981-4997
Published 2022-8-1
DOI 10.1111/febs.16412
PMID 35202511
MeSH Alkyl and Aryl Transferases* Mycobacterium* / genetics Neoprene Oxidoreductases / genetics Terpenes
IF 4.392
General Microbes JCM 13017, JCM 6377, JCM 6376, JCM 6366, JCM 7439, JCM 6371, JCM 6375, JCM 6364, JCM 6367, JCM 6370, JCM 6362