Natural products (NPs) have a long history as a source of, and inspiration for, novel agrochemicals. Many of the existing herbicides, fungicides, and insecticides have their origins in a wide range of NPs from a variety of sources. Owing to the changing needs of agriculture, shifts in pest spectrum, development of resistance, and evolving regulatory requirements, the need for new agrochemical tools remains as critical as ever. As such, NPs continue to be an important source of models and templates for the development of new agrochemicals, demonstrated by the fact that NP models exist for many of the pest control agents that were discovered by other means. Interestingly, there appear to be distinct differences in the success of different NP sources for different pesticide uses. Although a few microbial NPs have been important starting points in recent discoveries of some insecticidal agrochemicals, historically plant sources have contributed the most to the discovery of new insecticides. In contrast, fungi have been the most important NP sources for new fungicides. Like insecticides, plant-sourced NPs have made the largest contribution to herbicide discovery. Available data on 2014 global sales and numbers of compounds in each class of pesticides indicate that the overall impact of NPs to the discovery of herbicides has been relatively modest compared to the impact observed for fungicides and insecticides. However, as new sourcing and approaches to NP discovery evolve, the impact of NPs in all agrochemical arenas will continue to expand. © 2016 Society of Chemical Industry.

With the anticipated population growth in the coming decades, the changing regulatory environment, and the continued emergence of resistance to commercial pesticides, there is a constant need to discover new lead chemistries with novel modes of action. We have established a portfolio of approaches to accelerate lead generation. One of these approaches capitalizes on the rich bioactivity of natural products (NPs), highlighted by the numerous examples of NP‐based crop protection compounds. Within Corteva Agriscience and the affiliated preceding companies, NPs have been a fruitful approach, for nearly three decades, to identifying and bringing to the market crop protection products inspired by or originating from NPs, . Included in these NP‐based crop protection products are the spinosyns family of insecticides, and those from more recent areas of NP‐based fungicidal chemistry, as highlighted in this perspective. © 2019 Society of Chemical Industry

Spinosyns, a novel class of insect active macrolides produced by Saccharopolyspora spinosa, are used for insect control in a number of commercial crops. Recently, a new class of spinosyns was discovered from S. pogona NRRL 30141. The butenyl-spinosyns, also called pogonins, are very similar to spinosyns, differing in the length of the side chain at C-21 and in the variety of novel minor factors. The butenyl-spinosyn biosynthetic genes (bus) were cloned on four cosmids covering a contiguous 110-kb region of the NRRL 30141 chromosome. Their function in butenyl-spinosyn biosynthesis was confirmed by a loss-of-function deletion, and subsequent complementation by cloned genes. The coding sequences of the butenyl-spinosyn biosynthetic genes and the spinosyn biosynthetic genes from S. spinosa were highly conserved. In particular, the PKS-coding genes from S. spinosa and S. pogona have 91-94% nucleic acid identity, with one notable exception. The butenyl-spinosyn gene sequence codes for one additional PKS module, which is responsible for the additional two carbons in the C-21 tail. The DNA sequence of spinosyn genes in this region suggested that the S. spinosa spnA gene could have been the result of an in-frame deletion of the S. pogona busA gene. Therefore, the butenyl-spinosyn genes represent the putative parental gene structure that was naturally engineered by deletion to create the spinosyn genes.

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The two genes required for proline utilization (put) in Salmonella typhimurium form a divergent operon. Extensive genetic evidence suggests that transcription of the put operon is autoregulated by the putA gene product, a membrane-associated dehydrogenase. In order to understand the mechanism of regulation, we characterized plasmid clones of the put operon. A 7.5 kb clone contains both of the put structural genes and regulatory sites. This clone only expressed two unique proteins corresponding to the putA and putP gene products. By comparing the physical and genetic maps of the put operon, the position of the put regulatory region was defined and the DNA sequence of this region was determined. Analysis of the DNA sequence indicated several potential regulatory sites for the put genes. Based on genetic and physical mapping studies, the most likely regulatory sites are two convergent promoters approximately 30 bp apart. A 27 bp palindrome located between the two promoters may be the operator for autoregulation by the PutA protein. The putA translational start site is 40 bp downstream of its putative mRNA start site. The putP promoter and its translational start site are separated by a 400 bp untranslated region.