The spinosyn family of insecticides: realizing the potential of natural products research

Abstract

The spinosyns are a large family of unprecedented compounds produced from fermentation of two species of Saccharopolyspora. Their core structure is a polyketide-derived tetracyclic macrolide appended with two saccharides. They show potent insecticidal activities against many commercially significant species that cause extensive damage to crops and other plants. They also show activity against important external parasites of livestock, companion animals and humans. Spinosad is a defined combination of the two principal fermentation factors, spinosyns A and D. Structure-activity relationships (SARs) have been extensively studied, leading to development of a semisynthetic second-generation derivative, spinetoram. The spinosyns have a unique mechanism of action (MOA) involving disruption of nicotinic acetylcholine receptors. When compared with many other insecticides, the spinosyns generally show greater selectivity toward target insects and lesser activity against many beneficial predators as well as mammals and other aquatic and avian animals. Their insecticidal spectrum, unique MOA and lower environmental effect make them useful new agents for modern integrated pest management programs. As a result, this work has received U S Presidential Green Chemistry Challenge Awards.

Oxidative stress and DNA damage induced by spinosad exposure in Spodoptera frugiperda Sf9 cells

“…Spinosad was previously thought to be a reduced-risk biopesticide by United States Environmental Protection Agency due to its selective toxicity to non-target species and the lower potential for environmental damage, which is widely used in agriculture and stockbreeding (Kirst, 2010). Until now, spinosad has been shown to be non-target toxicity, the molecular mechanism has been paying more and more attention (Biondi et al, 2012).…”

Biopesticides from Natural Products: Current Development, Legislative Framework, and Future Trends

“…However, it is relatively simple to generate many similar chemical structures, using either chemical or biochemical pathways. Thus, the MoA of these compounds can be studied using an approximation of the structure-activity relationship (SAR) (Tewary et al 2006;Bhardwaj et al 2010;Kirst 2010;Li et al 2013). This term describes a rapidly growing field of research that studies relationships between molecular structure (e.g., available hydroxyl (He et al 1997) or polymerization degree (Frackenpohl et al 2009)) and the physicochemical and biological response.…”

“…Tewary et al (2006) carried out a similar work with Aphis craccivora, and they observed that the position of double bonds in the C6-C3 system is important because it influences mitochondrial respiration; increasing the activity of phenylpropanoids by nonpolar substitutes such as methoxy groups enhances its penetration through the body cuticle and diffusion. In the spinosyn family, over 1000 analogs have been obtained and tested (Salgado and Sparks 2005), and their SARs have been evaluated (Kirst 2010). 1.…”

Microbial agents against Helicoverpa armigera: Where are we and where do we need to go?

“…Several studies have shown that spinosyn has no long time persistence ability in plants, soil and other environments due to facile degradation by microbes present, whereby they partition them into organic matter and sediment with subsequent biotic degradation in the absence of light. Overall, they are easily subjected to diverse degradative pathways and metabolic mechanisms, and hence reduce their persistence in plants, and other environments (Kirst, 2010).…”