The spinosyns, spinosad, spinetoram, and synthetic spinosyn mimics ‐ discovery, exploration, and evolution of a natural product chemistry and the impact of computational tools

Abstract

Natural products (NPs) have long been a source of insecticidal crop protection products. Like many macrolide NPs, the spinosyns originated from a soil inhibiting microorganism (Saccharopolyspora spinosa). More than 20 years after initial registration, the spinosyns remain a unique class of NP‐based insect control products that presently encompass two insecticidal active ingredients, spinosad, a naturally occurring mixture of spinosyns, and spinetoram, a semi‐synthetic spinosyn product. The exploration and exploitation of the spinosyns has, unusually, been tied to an array of computational tools including artificial intelligence (AI)‐based quantitative structure activity relationship (QSAR) and most recently computer‐aided modeling and design (CAMD). The AI‐based QSAR directly lead to the discovery of spinetoram, while the CAMD studies have recently resulted in the discovery and building of a series of synthetic spinosyn mimics. The most recent of these synthetic spinosyn mimics show promise as insecticides targeting lepidopteran insect pests as demonstrated by field studies wherein the efficacy has been shown to be comparable to spinosad and spinetoram. These and a range of other aspects related to the exploration of the spinosyns over the past 30 years are reviewed herein. © 2020 Society of Chemical Industry

Understanding the biological action of insecticides is the key to their continuous improvement

“…The 2019 Spencer awardee, Thomas Sparks, prepared an insightful review based on his award address 1 . This paper describes his career‐long interest in natural product chemistry, and how developments in computational approaches have and will continue to aid discovery of new insecticides.…”

Success, despite another plague year

“…A rationale for trehalase as a new fungicide and insecticide target is provided, 11 as are the Cys‐loop family of ligand‐gated ion channels for new insecticides 12 . Discovery and future of spinosyns, spinosad, spinetoram, and synthetic spinosyn mimics are reviewed 13 . Swevers et al .…”

Bacterioferritin: a key iron storage modulator that affects strain growth and butenyl-spinosyn biosynthesis in Saccharopolyspora pogona

“…Soil microbial actinomycetes can produce a variety of secondary metabolites, many of which are biologically active natural products that have important application value in industry, medicine and agriculture, and are valuable resources for human development and utilization [ 1 – 3 ]. Butenyl-spinosyn, a secondary metabolite produced by the aerobic fermentation of the soil actinomycete Saccharopolyspora pogona , is a spinosyn structural analog [ 4 ], that effectively kills pests by paralyzing the nervous system of insects [ 5 ].This unique insecticidal mechanism makes it powerful in the insecticidal spectrum, harmless to humans and animals, environmentally friendly, safe as a biological pesticide and as a chemical pesticide, giving it broad application prospects in agriculture [ 6 , 7 ].…”