Engineered yeast facilitates rapid and systematic mining of fungal chimeric terpene synthases

doi:10.12211/2096-8280.2021-084

Synthetic Biology Journal ›› 2021, Vol. 2 ›› Issue (5): 666-673.DOI: 10.12211/2096-8280.2021-084

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Engineered yeast facilitates rapid and systematic mining of fungal chimeric terpene synthases

FAN Zhen¹^,², PAN Haixue¹^,², TANG Gongli¹^,²

^1.School of Chemistry and Materials Science，Hangzhou Institute for Advanced Study，University of Chinese Academy of Sciences，Hangzhou 310024，Zhejiang，China
^2.State Key Laboratory of Bio-Organic and Natural Products Chemistry，Shanghai Institute of Organic Chemistry，Chinese Academy of Sciences，Shanghai 200032，China

Received:2021-08-13 Revised:2021-08-29 Online:2021-11-19 Published:2021-10-31
Contact: TANG Gongli

工程酵母助力真菌嵌合萜类合酶的快速系统挖掘

范震¹^,², 潘海学¹^,², 唐功利¹^,²

^1.中国科学院大学杭州高等研究院，化学与材料科学学院，浙江杭州 310024
^2.中国科学院上海有机化学研究所，生命有机化学国家重点实验室，上海 200032

通讯作者: 唐功利
作者简介:范震（1987—），男，博士，博士后，主要从事天然产物生物合成研究。E-mail：fanzhen@sioc.ac.cn
唐功利（1971—），男，博士，研究员，主要从事天然产物生物合成和化学生物学研究。E-mail：gltang@sioc.ac.cn
基金资助:
国家自然科学基金重点项目(31930002)

Abstract

Abstract:

Chimeric terpene synthases (PTTSs), which consist of C-terminal prenyltransferase (PT) and N-terminal ClassⅠterpene synthase (TS) domains, are unique to fungi for catalyzing the synthesis of structurally diverse diterpenes and sesterterpenes. Since the first PTTS was discovered in 2007, only about 20 PTTSs have been functionally verified, and understanding of the origin and functional evolution of PTTS genes is very limited. Recently, Professor Tiangang Liu's research team at Wuhan University and Professor Feng Chen's research team at the University of Tennessee in the United States have conducted in-depth exploration on the origin and functional evolution of PTTS with an efficient terpene precursor yeast chassis system combined with the high-throughput automatic screening platform. The research not only expands the chimeric terpene synthase family, but also provides an advanced method for mining more terpene synthases for the biosynthesis of terpenoids.

Key words: biosynthesis, chimeric terpene synthase, evolution, terpenoids, yeast chassis

摘要：

真菌特有的嵌合萜类合酶（简称为PTTS）由C端异戊烯基转移酶（PT）结构域和N端I型萜类合酶（TS）结构域组成，可直接催化异戊二烯单元产生结构多样的二萜和二倍半萜化合物。自2007年发现第一个PTTS以来，只有约20个PTTS的功能被验证，人们对PTTS的起源和功能进化的认识还十分有限。最近武汉大学刘天罡教授课题组与美国田纳西大学陈峰教授课题组合作，运用高效萜类前体供给的酿酒酵母底盘并结合高通量的自动化平台，对PTTS的起源和功能进化进行了深入系统的探索，扩充了嵌合萜类合酶家族成员的数量，并为萜类化合物的挖掘提供了一个高效的方法。

关键词: 生物合成, 嵌合萜类合酶, 进化, 萜类, 酵母底盘

CLC Number:

FAN Zhen, PAN Haixue, TANG Gongli. Engineered yeast facilitates rapid and systematic mining of fungal chimeric terpene synthases[J]. Synthetic Biology Journal, 2021, 2(5): 666-673.

范震, 潘海学, 唐功利. 工程酵母助力真菌嵌合萜类合酶的快速系统挖掘[J]. 合成生物学, 2021, 2(5): 666-673.

Figures/Tables 6

Fig. 1 Formation of terpenoid skeletons through the catalysis by isopentenyl transferase (PT) and terpene synthase (TS)

Fig. 2 Two cases for cyclization catalyzed by TypeⅠand TypeⅡterpene synthases (TSs)

Fig. 3 Catalytic reactions of 4 chimeric terpene synthases

Fig. 4 Two cyclization reactions catalyzed by PTTS

Fig. 5 Synthesis of artemisinin and (-)-englerin A by metabolic engineering combined with synthetic chemistry

Fig. 6 Terpenoids and their structures synthesized under the catalysis of 54 PTTSs(Previously reported PTTSs and resulting products are marked in red, and 24 newly identified PTTSs by Liu Tiangang et al and resulting products are marked in pink. Products from plants and microorganisms are marked in green and blue, respectively)

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Engineered yeast facilitates rapid and systematic mining of fungal chimeric terpene synthases

工程酵母助力真菌嵌合萜类合酶的快速系统挖掘

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