Structural-model-based genome mining can efficiently discover novel non-canonical terpene synthases hidden in genomes of diverse species

被引：1

作者：

Abe, Tohru ^{[1
]}

Shiratori, Haruna ^{[1
]}

Kashiwazaki, Kosuke ^{[2
]}

Hiasa, Kazuma ^{[3
]}

Ueda, Daijiro ^{[1
]}

Taniguchi, Tohru ^{[4
]}

Sato, Hajime ^{[3
,5
]}

Abe, Takashi ^{[2
]}

Sato, Tsutomu ^{[1
]}

机构：

[1] Niigata Univ, Grad Sch Sci & Technol, Dept Life & Food Sci, Ikarashi 2-8050,Nishi ku, Niigata 9502181, Japan

[2] Niigata Univ, Grad Sch Sci & Technol, Dept Elect & Informat Engn, Ikarashi 2-8050,Nishi ku, Niigata 9502181, Japan

[3] Univ Yamanashi, Interdisciplinary Grad Sch Med & Engn, 4-4-37 Takeda, Kofu, Yamanashi 4008510, Japan

[4] Hokkaido Univ, Fac Adv Life Sci, Frontier Res Ctr Adv Mat & Life Sci, North 21 West 11, Sapporo 0010021, Japan

[5] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan

来源：

CHEMICAL SCIENCE | 2024年 / 15卷 / 27期

基金：

日本学术振兴会;

关键词：

All Open Access; Gold;

D O I：

10.1039/d4sc01381f

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Non-canonical terpene synthases (TPSs) with primary sequences that are unrecognizable as canonical TPSs have evaded detection by conventional genome mining. This study aimed to prove that novel non-canonical TPSs can be efficiently discovered from proteins, hidden in genome databases, predicted to have 3D structures similar to those of class I TPSs. Six types of non-canonical TPS candidates were detected using this search strategy from 268 genome sequences from actinomycetes. Functional analyses of these candidates revealed that at least three types were novel non-canonical TPSs. We propose classifying the non-canonical TPSs as classes ID, IE, and IF. A hypothetical protein MBB6373681 from Pseudonocardia eucalypti (PeuTPS) was selected as a representative example of class ID TPSs and characterized. PeuTPS was identified as a diterpene synthase that forms a 6/6/6-fused tricyclic gersemiane skeleton. Analyses of PeuTPS variants revealed that amino acid residues within new motifs [D(N/D), ND, and RXXKD] located close to the class I active site in the 3D structure were essential for enzymatic activity. The homologs of non-canonical TPSs found in this study exist in bacteria as well as in fungi, protists, and plants, and the PeuTPS gene is not located near terpene biosynthetic genes in the genome. Therefore, structural-model-based genome mining is an efficient strategy to search for novel non-canonical TPSs that are independent of biological species and biosynthetic gene clusters and will contribute to expanding the structural diversity of terpenoids. Non-canonical terpene synthases with primary sequences that are unrecognizable as canonical terpene synthases could be discovered through structural-model-based genome mining.

引用

页码：10402 / 10407

页数：6