Recent Findings on the Multifaceted Functionality of Enzyme Inhibition by Natural Compounds: A Review

John   Paul   Delano-Frier; Jose   Luis   Castro-Guillen; Alejandro      Blanco-Labra

Abstract

Enzyme inhibition is a fundamental process to preserve the orderly sequence of events required for life, from seed germination to apoptosis. This review will verse on recent findings showing the various ways in which enzyme inhibition has been incorporated into the arsenal of many organisms, either as an effective defensive weapon or as a factor needed for the establishment of infection, parasitism and/or symbiotic associations, and how this diverse functionality can be exploited for therapeutic uses. It will describe several non-proteinaceous enzyme inhibitors isolated from natural sources or synthesized on the basis of structural or functional similarity to biosynthetic enzymes that have been employed for effective treatment against infections and/or aggresive diseases, such as cancer and AIDS, given their ability to disrupt critical functions of the target organisms or malignant cells. A relation of novel plant proteinase inhibitors (PPIs) with multiple and/or novel functions or engineered to have a highly selectivity on their target enzymes in order to avoid deleterious effects in a multi-trophic level that negatively affect insect pollinators or predators, is included too. This development could eliminate or reduce one of the most pressing concerns about the use of PIs as transgenes in many important crops. Finally, an account of the highly specific inhibition of enzymatic activity by biotechnological (e.g. gene silencing) or biochemical means, which have proven to be powerful tools to reveal novel functions for a variety of enzymes will be made in the context of defense, development, senescence and programmed cell death in plants.

Keywords: Proteinase inhibitors, programmed cell death, developmental cell death, defense, pathogen effectors, therapeutic agents, evolution, gene silencing, cancer, HIV