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Publication Date


First Advisor

Cristina Suarez

Document Type

Honors Project

Degree Name

Bachelor of Arts




Diels-Alderase, PyrE3, Steroselectivity, QM calculation


Catalytic mechanisms for Diels-Alder reaction have been of great interest to researchers even before the discovery of the first natural Diels-Alderase. [1] Many efforts to isolate a standalone natural Diels-Alderase have been successful, and several such Diels-Alderases have been crystallized, but their catalytic mechanisms are not always clear. In 2018, Wen Liu and coworkers [2] crystallized a new natural Diels-Alderase, known as PyrE3, in the biosynthetic pathway for pyrroindomycins. PyrE3 is a mono-functional Diels-Alderase that catalyzes an intramolecular [4+2] cycloaddition, which turns a linear polyene intermediate into a bis-fused cyclic system as shown in Figure 1. During the catalysis, PyrE3 enzyme controls the product stereochemistry and allows the intramolecular Diels-Alder reaction, which has proven inert in the absence of PyrE3.


Figure 1: PyrE3 catalyzes an intramolecular Diels-Alder reaction in PYR biosynthetic pathway that turns a linear polyene intermediate into a decalin.

In this study, we aim to investigate the catalysis of PyrE3 in two directions: 1) to unravel how PyrE3 reduces the activation barrier to make the reaction happen and enhance the reaction rate; 2) to explain the origin of its stereoselectivity. The main investigative approaches in this study include quantum mechanical calculations, protein-ligand dockings and theozyme calculations.


©2019 Xingyi Guan. Access limited to the Smith College community and other researchers while on campus. Smith College community members also may access from off-campus using a Smith College log-in. Other off-campus researchers may request a copy through Interlibrary Loan for personal use.




xviii, 95 pages : illustrations (some color). Includes bibliographical references (pages 89-95)