title: Defining the Product Chemical Space of Monoterpenoid Synthases.
abstract: Terpenoid synthases create diverse carbon skeletons by catalyzing complex carbocation rearrangements, making them particularly challenging for enzyme function prediction. To begin to address this challenge, we have developed a computational approach for the systematic enumeration of terpenoid carbocations. Application of this approach allows us to systematically define a nearly complete chemical space for the potential carbon skeletons of products from monoterpenoid synthases. Specifically, 18758 carbocations were generated, which we cluster into 74 cyclic skeletons. Five of the 74 skeletons are found in known natural products; some of the others are plausible for new functions, either in nature or engineered. This work systematizes the description of function for this class of enzymes, and provides a basis for predicting functions of uncharacterized enzymes. To our knowledge, this is the first computational study to explore the complete product chemical space of this important class of enzymes.
authors: Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, San Francisco, California, United States of America.|California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, California, United States of America.
authors: Boxue
authors: B
authors: Tian
authors: Department of Chemistry, University of Utah, Salt Lake City, Utah, United States of America.
authors: C Dale
authors: CD
authors: Poulter
authors: Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, San Francisco, California, United States of America.|California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, California, United States of America.
authors: Matthew P
authors: MP
authors: Jacobson
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D019295:Computational Biology; D008958:Models, Molecular; D008968:Molecular Conformation; D039821:Monoterpenes / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D039821:Monoterpenes; D019883:Alkyl and Aryl Transferases; C108877:terpene synthase