Open AccessFrom a Biosynthetic Pathway toward a Biocatalytic Process and Chemocatalytic Modifications: Three‐Step Enzymatic Cascade to the Plant Metabolite cis ‐(+)‐12‐OPDA and Metathesis‐Derived Products
Author(s) -
Löwe Jana,
Dietz KarlJosef,
Gröger Harald
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201902973
Subject(s) - biocatalysis , chemistry , metathesis , oxylipin , alkene , kinetic resolution , combinatorial chemistry , metabolite , stereochemistry , enzyme , organic chemistry , enantioselective synthesis , biochemistry , reaction mechanism , catalysis , polymerization , polymer
A biotechnological approach toward the plant metabolite and regulator cis ‐(+)‐12‐oxophytodienoic acid ( cis ‐(+)‐12‐OPDA) in a one‐pot process with >99% conversion, at least 90% selectivity and ≤10% of side products as well as a high diastereoselectivity (leading to d.r. of at least 90:10) is reported. The optimized organic‐synthetic enzyme cascade for preparing this bioactive and commercial molecule with pharmaceutical relevance on a gram per L scale is designed based on its biosynthetic pathway starting from cheap and readily accessible linolenic acid. Toward this end, a recombinant biocatalyst system has been prepared for carrying out the most critical two key steps in a tailored manner, thus avoiding sensitive intermediate decomposition. Furthermore, cis ‐(+)‐12‐OPDA is successfully modified via a cross‐alkene metathesis reaction with conversions of up to >99%, leading to a compound library of new cis ‐(+)‐12‐OPDA derivatives with different substitution pattern of the side chain at the 2‐position. By means of such a combined biotechnological and chemocatalytic route, a straightforward approach to a structurally unique oxylipin library is realized, which would be highly difficult or not accessible by pure chemical and biotechnological methods, respectively.