Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis

被引：149

作者：

Andersen-Ranberg, Johan ^{[1
]}

Kongstad, Kenneth Thermann ^{[2
]}

Nielsen, Morten Thrane ^{[1
]}

Jensen, Niels Bjerg ^{[3
]}

Pateraki, Irini ^{[1
]}

Bach, Soren Spanner ^{[1
]}

Hamberger, Britta ^{[1
]}

Zerbe, Philipp ^{[4
]}

Staerk, Dan ^{[2
]}

Bohlmann, Jorg ^{[5
]}

Moller, Birger Lindberg ^{[1
]}

Hamberger, Bjorn ^{[1
]}

机构：

[1] Ctr Synthet Biol, Dept Plant & Environm Sci, DK-1871 Copenhagen, Denmark

[2] Univ Copenhagen, Nat Prod Res, DK-1168 Copenhagen, Denmark

[3] Evolva AS, Copenhagen, Denmark

[4] Univ Calif Davis, Dept Plant Biol, Davis, CA USA

[5] Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2016年 / 55卷 / 06期

基金：

加拿大自然科学与工程研究理事会;

关键词：

biosynthesis; biocatalysis; combinatorial biosynthesis; cyclizations; terpenes; SYNTHASES; METABOLISM; DISCOVERY; MANOOL; GENES;

D O I：

10.1002/anie.201510650

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

Plant-derived diterpenoids serve as important pharmaceuticals, food additives, and fragrances, yet their low natural abundance and high structural complexity limits their broader industrial utilization. By mimicking the modularity of diterpene biosynthesis in plants, we constructed 51 functional combinations of classI and II diterpene synthases, 41 of which are new-to-nature. Stereoselective biosynthesis of over 50 diterpene skeletons was demonstrated, including natural variants and novel enantiomeric or diastereomeric counterparts. Scalable biotechnological production for four industrially relevant targets was accomplished in engineered strains of Saccharomyces cerevisiae.

引用

页码：2142 / 2146

页数：5

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