Discovery and Reconstitution of the Cycloclavine Biosynthetic Pathway-Enzymatic Formation of a Cyclopropyl Group

被引：52

作者：

Jakubczyk, Dorota ^{[1
]}

Caputi, Lorenzo ^{[1
]}

Hatsch, Anaelle ^{[2
]}

Nielsen, Curt A. F. ^{[2
]}

Diefenbacher, Melanie ^{[2
]}

Klein, Jens ^{[2
]}

Molt, Andrea ^{[3
]}

Schroeder, Hartwig ^{[3
]}

Cheng, Johnathan Z. ^{[1
]}

Naesby, Michael ^{[2
]}

O'Connor, Sarah E. ^{[1
]}

机构：

[1] John Innes Ctr, Dept Biol Chem, Norwich, Norfolk, England

[2] Evolva SA, Reinach, Switzerland

[3] BASF SE, Ludwigshafen, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2015年 / 54卷 / 17期

基金：

英国生物技术与生命科学研究理事会;

关键词：

biosynthesis; cyclopropyl group; ergot alkaloids; natural products; pathway reconstitution; OLD YELLOW ENZYME; ASPERGILLUS-FUMIGATUS; ERGOT ALKALOIDS; LYSERGIC-ACID; BRANCH POINT; EXPRESSION; JAPONICUS; FAMILY;

D O I：

10.1002/anie.201410002

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The ergot alkaloids, a class of fungal-derived natural products with important biological activities, are derived from a common intermediate, chanoclavine-I, which is elaborated into a set of diverse structures. Herein we report the discovery of the biosynthetic pathway of cycloclavine, a complex ergot alkaloid containing a cyclopropyl moiety. We used a yeast-based expression platform along with in vitro biochemical experiments to identify the enzyme that catalyzes a rearrangement of the chanoclavine-I intermediate to form a cyclopropyl moiety. The resulting compound, cycloclavine, was produced in yeast at titers of >500 mgL(-1), thus demonstrating the feasibility of the heterologous expression of these complex alkaloids.

引用

页码：5117 / 5121

页数：5

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