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Identification and functional analysis of a new type of Z,E-mixed prenyl reductase from mycobacteria
The FEBS Journal ( IF 5.5 ) Pub Date : 2022-02-24 , DOI: 10.1111/febs.16412 Tohru Abe 1 , Mariko Hakamata 2 , Akihito Nishiyama 2 , Yoshitaka Tateishi 2 , Sohkichi Matsumoto 2 , Hisashi Hemmi 3 , Daijiro Ueda 1 , Tsutomu Sato 1
The FEBS Journal ( IF 5.5 ) Pub Date : 2022-02-24 , DOI: 10.1111/febs.16412 Tohru Abe 1 , Mariko Hakamata 2 , Akihito Nishiyama 2 , Yoshitaka Tateishi 2 , Sohkichi Matsumoto 2 , Hisashi Hemmi 3 , Daijiro Ueda 1 , Tsutomu Sato 1
Affiliation
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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.
中文翻译：
一株新型Z,E-混合异戊二烯还原酶的鉴定及功能分析
在各种生物体中发现了具有减少的Z,E-混合异戊二烯基团的类异戊二烯。迄今为止，只有参与多酚生物合成的聚异戊二烯醇还原酶 (PR-Dol) 已被鉴定为能够还原Z，E-混合异戊二烯基团的酶。尽管在分枝杆菌中发现了具有减少的Z,E-混合异戊二烯基团的 C 35 -类异戊二烯，但Z ,E-混合七异戊二烯基还原酶 (HepR) 仍未确定。在本研究中，进行了 HepR 的鉴定和功能分析。在万巴氏分枝杆菌基因组中未检测到PR-Dol同源基因。然而，香叶基香叶基还原酶 (GGR) 的同源物，它与全E异戊二烯基作为底物，在基因组中被编码；因此，我们将其分析为 HepR 候选者。体外酶学测定和体内基因抑制分析确定 GGR 同源物为 HepR，并揭示 HepR 催化Z,E-混合七异戊二烯基二磷酸中 ω-和E-异戊二烯基单元的还原，并且 C 35 -类异戊二烯主要使用E生物合成,E,E-香叶基香叶基二磷酸作为前体。因此，证明Z，E-混合异戊二烯还原酶家族存在于GGR同源物中。据我们所知，这是首次发现一种新型Z,E-与PR-Dol没有序列同源性的混合异戊二烯还原酶。HepR的底物特异性与GGR显着不同，表明它是一种新酶。HepR 同源物广泛分布在分枝杆菌基因组中，脂质分析表明，包括致病物种在内的许多菌株都产生 HepR 代谢物。这种新酶的发现将促进对Z、E-混合类异戊二烯的进一步研究。
更新日期：2022-02-24
中文翻译：
一株新型Z,E-混合异戊二烯还原酶的鉴定及功能分析
在各种生物体中发现了具有减少的Z,E-混合异戊二烯基团的类异戊二烯。迄今为止，只有参与多酚生物合成的聚异戊二烯醇还原酶 (PR-Dol) 已被鉴定为能够还原Z，E-混合异戊二烯基团的酶。尽管在分枝杆菌中发现了具有减少的Z,E-混合异戊二烯基团的 C 35 -类异戊二烯，但Z ,E-混合七异戊二烯基还原酶 (HepR) 仍未确定。在本研究中，进行了 HepR 的鉴定和功能分析。在万巴氏分枝杆菌基因组中未检测到PR-Dol同源基因。然而，香叶基香叶基还原酶 (GGR) 的同源物，它与全E异戊二烯基作为底物，在基因组中被编码；因此，我们将其分析为 HepR 候选者。体外酶学测定和体内基因抑制分析确定 GGR 同源物为 HepR，并揭示 HepR 催化Z,E-混合七异戊二烯基二磷酸中 ω-和E-异戊二烯基单元的还原，并且 C 35 -类异戊二烯主要使用E生物合成,E,E-香叶基香叶基二磷酸作为前体。因此，证明Z，E-混合异戊二烯还原酶家族存在于GGR同源物中。据我们所知，这是首次发现一种新型Z,E-与PR-Dol没有序列同源性的混合异戊二烯还原酶。HepR的底物特异性与GGR显着不同，表明它是一种新酶。HepR 同源物广泛分布在分枝杆菌基因组中，脂质分析表明，包括致病物种在内的许多菌株都产生 HepR 代谢物。这种新酶的发现将促进对Z、E-混合类异戊二烯的进一步研究。
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