Prodigiosin: A Potential Eco-Friendly Insecticide for Sustainable Crop Protection

Abstract

Globally, insect pests adversely affect approximately 75% of the most important crops. However, the widespread use of chemical insecticides has significant drawbacks, including non-specific biological activity, toxicity to humans, detrimental effects on beneficial insects, and the rapid development of resistance. In this context, prodigiosin—a tripyrrolic secondary metabolite produced by various microorganisms—emerges as a promising alternative due to its favourable properties, such as being non-toxic, environmentally safe, non-irritant, and non-allergenic, and having non-carcinogenic potential. Prodigiosin has demonstrated insecticidal efficiency against pests at various developmental stages. Studies suggest that prodigiosin inhibits enzymes like acetylcholine esterase, protease, and acid phosphatase and induces oxidative stress. This review explores the potential of prodigiosin as an eco-friendly insecticide, discussing its production, extraction, and purification processes and its advantages, disadvantages, and mechanism of action, and future perspectives. Special emphasis is given to using non-pathogenic strains to mitigate biosafety concerns.

1. Introduction

Prodigiosin is a pyrrolic class of secondary metabolite compound, specifically a tripyrrol. It is characterized by two interconnected rings linked to a third ring via a methane bridge, differentiating it from other structurally related molecules [1]. Microbial secondary metabolites are known for being a rich source of bioactive compounds and are, therefore, widely utilized in the health, food, and biotechnology sectors. Pyrrolic compounds—including prodigiosin—contain ring structures with electron-rich regions that enable the formation of hydrogen bonds and metal coordination. Figure 1 (from Mnif et al. [2]) depicts the chemical structure of prodigiosin, which is notable for its ability to change colour in response to pH variations, lending it wide-ranging applications [3].

Prodigiosin is primarily produced by the Gram-negative, facultatively anaerobic bacterium Serratia marcescens [4], although various other Gram-negative and Gram-positive microorganisms can also synthesize it. This highly hydrophobic pigment exhibits an extensive spectrum of biological activities, including antibacterial, antifungal, algicidal, antiprotozoal, antiparasitic, antiparasitic, immunosuppressive, and anticancer properties [5]. Despite its broad bioactivity, S. marcescens is recognized as an opportunistic pathogen [6]. Evidence suggests that prodigiosin confers ecological advantages to S. marcescens; for instance, Haddix and Shanks found that pigmented cells produce twice as much biomass as non-pigmented cells [6]. Additionally, Yip et al. discovered that prodigiosin helps S. marcescens compete against pathogenic bacteria—such as methicillin-resistant strains of Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella enterica serovar Typhimurium, Enterococcus faecalis, and Escherichia coli—through the inhibition of protease secretion, biofilm formation, and overall bacterial growth [7].

Prodigiosin synthesis typically occurs in cells grown aerobically at temperatures up to 32 °C. Nutritional factors, such as phosphate limitation and glucose concentration, strongly influence pigment production via mechanisms including cyclic AMP signalling and quorum sensing [6]. Beyond S. marcescens, other species of the genus are known to produce this pigment, including S. marcescens [8], S. plymuthica [9], and S. rubidaea [10]. Additionally, other known genera to produce prodigiosin include Pseudoalteromonas [11,12], Hahella [13], Janthinobacterium [14], Pseudomonas [5,15], Vibrio [16], and Streptomyces [5,17,18].

Numerous studies highlight the multifaceted applications of prodigiosin. It is an immunomodulator in cancer therapy [19], a photosensitizer [20], and a synergistic agent when combined with nanoparticles [21]. Additionally, prodigiosin shows potent antimalarial and antiviral activities [22]. It has also been employed in environmental restoration efforts, specifically inhibiting harmful algal blooms [23]. Recent findings suggest that prodigiosin may be pivotal in controlling agricultural insect pests [24,25,26,27,28,29,30,31], positioning it as a prospective eco-friendly alternative to conventional pesticides.

2. Production, Extraction, and Purification of Prodigiosin

2.1. Production Conditions

Most studies investigating prodigiosin’s insecticidal properties utilize Serratia marcescens [24,25,26,27,28]. Typically, cultures are maintained at around 30 °C, with peptone as the most common nitrogen source [26,27,28,29,30], and varied carbon sources—such as sucrose, glycerol, mannitol, and even squid pen powder [25]. Despite its prominence, S. marcescens is an opportunistic pathogen [6], raising safety concerns for large-scale production.

Fortunately, Streptomyces coelicolor [32] and other non-pathogenic bacteria can also synthesize prodigiosin, an avenue worth exploring to reduce biosafety risks. Moreover, sustainable production strategies have been reported. For example, soybean oil and agro-industrial wastes (e.g., soybean meal, wheat bran) have been successfully utilized as substrates, achieving high yields of prodigiosin and simultaneously valorizing industrial byproducts [33,34]. Some other eco-friendly strategies to produce prodigiosin can be assessed. For example, Nguyen et al. used fish head powder as a carbon and nitrogen source in the fermentation process with strains of Serratia marcescens TNU01 in a bioreactor of 14 L. Combined with crude chitin in a ratio of 9/1 and supplemented with 0.05% Ca₃(PO₄)₂ and 0.03% K₂SO₄, the highest yield was 6.4 mg mL⁻¹ in 10 h of fermentation [35].

In another study, Aruldass et al. used brown sugar as a low-cost growth medium for the production of pigment, using a strain of Serratia marcescens UTM1 in a bioreactor of 5 L, a concentration of brown sugar of 10%, a temperature of 25 °C, an incubation time of 24 h, at 200 rpm, achieving a high yield of 8000 mg L⁻¹ [36]. As mentioned before, prodigiosin can also be produced by species like Streptomyces coelicolor. For example, Tran et al. reused cassava wastewater and a strain of Serratia marcescens TNU01 in a bioreactor of 14 L in a growth medium with 0.25% casein, 0.05% MgSO₄, and 0.1% K₂HPO₄, with a temperature of 28 °C, during 8 h. In this study, the authors yielded 6150 mg L⁻¹ [37]. The studies mentioned demonstrate that prodigiosin can be produced with low-cost materials as a source of nutrients.

2.2. Extraction and Purification Methods

Given prodigiosin’s hydrophobic nature, organic solvents—methanol, ethanol, acetone, chloroform, and acidified ethanol—are commonly used for extraction [24,28,29,31]. Purification often involves thin-layer chromatography (TLC) [24,25,26,28], although other techniques, like high-performance liquid chromatography (HPLC) [31] and silica gel column chromatography [29], are also effective. While these methods yield high-purity prodigiosin, they frequently employ toxic solvents, underscoring the need for greener, more sustainable purification approaches. As a hydrophobic compound, eco-friendly lipophilic compounds could be used to extract prodigiosin. For example, this class of compounds could be extracted with enzymes, oils from various seeds, and pressurized liquids, combined with the assistance of ultrasound, microwave irradiation, and pulsed electric field extraction to reduce the use of solvents [38]. There is evidence of the efficacy of the sonication for the extraction of prodigiosin. For example, Sun et al. optimized the extracted prodigiosin from an Serratia marcescens jx1 strain, with extraction yields of 4.3 g ± 0.02 g from 100 g of dried cells, with a temperature of 23.4 °C, during 17.5 min, using acid acetone, with a solvent to solute ratio of 1:27.2 [39]. In another study, Khanam and Chandra extracted prodigiosin from Serratia marcescens and achieved a purity of 98.1 ± 1.7% using sonication at 60 °C, ethanol at 96% as a solvent, and a time of extraction of 6 min [40]. As can be seen, extraction techniques have a lot of unexploited potential.

3. Common Strategies for Insect Control

Insect pests significantly affect agriculture and the global food supply. Insects—the most diverse group of animals—are integral to ecosystem functions like seed dispersal, pollination, nutrient cycling, and population control by predation or parasitism mechanisms [41,42]. Approximately 75% of the world’s most important crop species rely on insects for pollination [41]. Nevertheless, in agricultural systems, insects can cause considerable losses, estimated at around 60–70% in tropical regions, especially in stored products [43]. Crops with economic importance, like wheat, are vulnerable to various pests, like the wheat weevil [44], aphids [44,45], wheat midges [46], cereal leaf beetle [47], grasshoppers [48], white grubs and termites [48,49], the hessian fly [50], armyworms [51], the wheat stem sawfly [52], the pink gramineous stem borer [53], and flea beetles [54]. Moreover, insects serve as vectors for major global diseases, including malaria [55], dengue [56], lymphatic filariasis [57], yellow fever [58], Japanese encephalitis, West Nile virus [59], chikungunya [60], Zika virus, and tularemia [60].

To address these challenges, pest control strategies generally fall into six main categories: cultural control, physical control, host resistance, mechanical control, chemical control, and biological control [61].

Table 1. Classification of insect control methods, according to the University of Wisconsin-Madison [61].

Cultural control: crop rotation, sanitation, trap cropping, selection of time of planting

Host resistance: improve plant characteristics that repel, tolerate, or kill pests

Physical controls: Use cardboard bands, glue board traps, and window screens to prevent pests from reaching hosts.

Mechanical control: directly remove or kill pests, like hand-picking

Biological control: use of beneficial organisms to control pests

Chemical control: use of chemicals to kill pests, repellants, irritants, synthetic pheromones, and insecticides

summarizes these methods. Given the drawback of many chemical insecticides—lack of specificity, human toxicity, non-target effects, and the development of resistant insect populations—prodigiosin has gained attention as a natural, eco-friendly control option that could be integrated with or replace traditional chemical approaches [62,63].

4. Insecticidal Activity of Prodigiosin and Mechanism of Action

4.1. Enzymatic Inhibition and Oxidative Stress

Over the past two decades, numerous studies have examined the insecticidal potential of prodigiosin. For instance, in a study, larvae from the fourth instar of Aedes aegypti were treated with prodigiosin, and alteration in key enzymes was observed. Esterase levels increased by 95.1%, while protease, acid phosphatase, and acetylcholine esterase activities decreased by 36, 12, 22, and 70%, respectively. Total protein content declined by 43.4% compared to the control, suggesting a multifaceted mechanism involving the disruption of enzymatic pathways [29]. The authors elucidated the mechanism of action: proteases typically play a role in developing resistance against toxins. However, a decrease in protease levels was noted in the test samples, which may be attributed to the non-proteic nature of prodigiosin. In contrast, resistant insects generally exhibit a high level of esterase activity. Non-specific esterases mediate this detoxification mechanism and are a key mechanism of insect resistance, which are likely to have contributed to the observed 95% increase in esterase levels in the test samples. In response to breaking down the neurotransmitter acetylcholine esterase at the synaptic cleft, nerve impulses can be transmitted across the gap. After a message is conveyed, neurotransmitters must be cleared promptly, and failure can lead to paralysis. In the mentioned study, acetylcholine esterase levels decreased in the prodigiosin-treated larvae by about 70% compared to the control group. Also, the quantity of acid phosphatase was decreased in the larvae treated with prodigiosin by 12%, compared to the control [29].

The hydrophobic nature of prodigiosin caused prodigiosin not to inhibit catalase and oxidase, but its hydrophobic nature (log P octanol-water value = 5.16) and capacity to induce oxidative stress contributed to its larvicidal action. Additionally, prodigiosin disrupted midgut alkalinization, dropping the midgut pH from above 10.5 to around 6 within 24 h [29]. Also, prodigiosin has different target sites, like single and double-strand DNA breaks, pH modulation, nitrogen-activated protein kinase regulation, and cell cycle progression inhibition, thus causing apoptosis [30].

4.2. Effectivity as Insecticide and Working Conditions

Table 2. Research works where prodigiosin was used for insect control.

Source/Production Conditions	Target Species/Working Conditions	Effectiveness/Dose or Concentration/Mechanism of Action	Reference
Serratia marcescens ATCC274. The strain was cultivated in a stainless steel tray using a 5% agar medium containing 0.5% bactopeptone and 1% glycerol at 30°C for 48 h. The bacteria were harvested and suspended in a physiological salt solution and centrifuged at 6000 rpm. The red pigments were then extracted using 95% ethanol, concentrated, and fractionated through thin-layer chromatography (TLC) with a solvent system of chloroform, methanol, and 5 M ammonia in a ratio of 80:25:4 (V/V).	Common cutworm Spodoptera litura and diamondback moth Plutella xylostella. Synergism ocurred with delta-endotoxin Cry 1C from Bacillus thuringiensis. The lethal activity of test samples was evaluated using 50 infested neonates, administering 1 µg g−1/diet of prodigiosin and 12 µg g−1/diet of Cry 1C over a treatment period of 7 days. Additionally, assays were conducted with prodigiosin alone at a concentration of 8 µg g−1/diet.	Prodigiosin and Cry 1C achieved 100% mortality in S. litura. There was 99% mortality in Plutella xylostella and 34% in S. litura at a dose of 8 µg g−1 The mechanism of action was not specified.	[28]
Serratia marcescens NMCC46. A loopful of 24 h-old culture was inoculated into nutrient broth media containing mannitol and incubated for 48 h at 30 ± 2 °C with continuous shaking at 120 rpm. Following this incubation period, the broth was acidified with 1% acidified ethanol and then centrifuged at 5000 rpm for 10 min. The supernatant was extracted using a water–chloroform mixture (1:1). The concentrated pigment was then dissolved in ethanol and purified using TLC.	Mosquitoes Aedes aegypti and Anopheles stephensi. Second, third, and fourth instar larvae of A. aegypti and A. stephensi were collected in four batches of ten and placed into 99 mL of water mixed with 1.0 mL of pigment. For the dose-response assay, 100 mL of the test solution were poured into 300 mL plastic cups, each containing ten larvae from the second, third, and fourth instar stages. The larvae were not fed during the treatment period. After 48 h of exposure, the number of dead larvae was recorded.	The lethal concentration values (LC50 and LC90) for the second, third, and fourth instars of A. aegypti are LC50 = 41.65, 139.51, 103.95 ppm; and LC90 = 117.81, 213.68, and 367.82 ppm. For A. stephensi, the values are LC50 = 51.12, 105.52, 133.07 ppm; and LC90 = 134.81, 204.45, and 285.35 ppm. Mortality begins at a concentration of 500 ppm, with signs of mortality observed within the first 6 h of exposure. More than 50% of the mortality occurs within the first 24 h. The mechanism of action was not specified.	[26]
Serratia marcescens TKU011. The pigment was produced using a medium containing 1.5% squid pen powder (SPP), supplemented with 0.1% K2HPO4 and 0.1% FeSO4(NH4)2SO4 · 6H2O. The cultivation was conducted at 30 °C for 24 h, followed by an additional two days at 25 °C. Four autoclave cycles were implemented throughout the process. Subsequently, the pigment was purified using TLC.	Oregon R strain of Drosophila melanogaster flies were reared in plastic vials containing standard fly medium with yeast, corn syrup, and agar, maintained at 25 °C and 60% humidity under a 12 h light–dark cycle. Eggs were collected from the flies during a 6 h period and preserved at the same temperature and humidity. After 72 h, the eggs were transferred to a 96-well tissue culture plate with 30 µL of standard fly medium, covered with a moistened paper filter disk infused with 230 ppm of prodigiosin, and kept at 25 °C. The number of surviving larvae was counted on the fifth day.	Lethal concentration causing 50% mortality in Drosophila larval (LC50) of PG was identified using a 5-day exposure period at a dose of 230 ppm. The mechanism of action was not specified.	[25]
Serratia nematodiphila 213C. A 50 mL fresh fermentation medium containing the following concentrations (g L−1), glycerol at 0.2 and peptone at 0.5, was prepared with a pH of 7.0 in 250 mL Erlenmeyer flasks. Each flask was inoculated with an inoculum that had an absorbance of 1.0 at 600 nm, at a concentration of 1% (v/v), and then incubated at 28 °C with shaking at 180 rpm for 72 h. Prodigiosine was purified through filtration using a glass wool-tied funnel or by centrifugation at 10,000 rpm for 15 min, and it was subsequently concentrated using a rotary vacuum evaporator at 50 °C under a vacuum of 10–5 torr.	Larvae of cotton bollworm Helicoverpa armigera and cotton leafworm Spodoptera litura. Second instar larvae were positioned in 12- or 24-well flat-bottom plates, utilizing pigment as their dietary feed. The plates were sealed and incubated in a humidified growth chamber set to 28 °C. The larvae were also placed on Petri dishes containing various concentrations of pigment applied to okra pods as food. The pigment’s larvicidal effect was assessed by counting the number of deceased larvae after 72 h and evaluating their motility through needle probing.	The mortality rates of the larvae of Helicoverpa armigera and Spodoptera litura were 70 and 100% when exposed to doses of 20 and 30 mg mL−1. The mechanism of action is likely to be due to a combination of factors, including the regulation of nitrogen-activated protein kinase, DNA damage, modulation of pH, and inhibition of the cell cycle.	[30]
Serratia marcescens NMCC 75. An active culture was inoculated into a medium containing sucrose and peptone and incubated for 24 h at 28 ± 2 °C. Following incubation, the culture was centrifuged at 7000× g for 10 min. The resulting cell pellet was suspended in methanol and centrifuged again. The crude pigment was then collected from the supernatant and heated to 90 °C. The dried pigment was re-dissolved in 2 mL of methanol and combined with 5 mL of sterile distilled water. After allowing the mixture to stand for 5 to 6 h, the pigment was separated on a silica gel column, with the elution performed using a hexane:methanol (1:2) solution.	Larval and pupal stages of mosquitoes of Aedes aegypti and Anopheles stephensi. Experiments were conducted at a temperature of 28 ± 2 °C and a relative humidity of 75–85%, following a light–dark cycle of 14:10 h. Bioassays were performed on early second, third, and fourth instar larvae. Twenty-five larvae from each stage were placed in a beaker containing 500 mL of dechlorinated tap water. For the initial screening, a concentration of 1 mg mL−1 was tested. Throughout a period of 6 to 24 h, the larvae were monitored for movement under an insect microscope. In the dose-response assay, various concentrations of prodigiosin were added to 100 mL of dechlorinated tap water, along with 25 larvae. Larval mortality was assessed over a period of 6 to 24 h. A similar methodology was applied to the pupae.	The LC50 values for the early second, third, fourth instar and pupal stages of A. aegypti were found to be 14 ± 1.2, 15.6 ± 1.48, 18 ± 1.3, and 21 ± 0.87 μg mL−1, respectively. For A. stephensi the LC50 values against the same stages were 19.7 ± 1.12, 24.7 ± 1.47, 26.6 ± 1.67, and 32.2 ± 1.79 μg mL−1, respectively. The mechanism of action involves the inhibition of the enzymes catalase, oxidase, carbonic anhydrase, and H+-V-ATPase.	[29]
Serratia sp. Peanut broth was inoculated with an overnight-grown culture of Serratia and incubated at 30 °C for 72 h. Following incubation, the mixture was centrifuged at 6000 rpm for 10 min. The pigment was extracted using acetone, methanol, or ethanol, and then centrifuged at 10,000 rpm for 10 min. Purification was carried out through TLC on silica gel G-60 F25, using a chloroform: methanol (95:5; v/v) mixture as the eluent.	The insecticidal efficacy was assessed through the application of a spray formulation targeting adult specimens of common household pests, including Periplaneta americana (American cockroach), Isoptera (termites), Dorymyrmex insanus (pyramid ants), and Solenopsis geminata (tropical fire ants).	100 % mortality was achived against cockroaches and tropical ants, while 85 to 71% effectiveness was noted with termites and pyramid ants when spraying prodigiosin (concentration not specified). The mechanism of action was not specified.	[24]
Serratia marcescens Se9. A 24 h culture was inoculated into 250 mL of nutrient broth medium and incubated at 30 °C for 48 h. Afterward, it was centrifuged at 1000 rpm for 15 min at 4 °C. The pellet was resuspended in acidified ethanol and vortexed for 5 min. It was then centrifuged at 10,000 rpm for 15 min, and the supernatant was transferred to a sterile 50 mL Falcon tube. Finally, the solvent was removed and the solution was concentrated using a rotary evaporator.	Larval and adult stages of yellow mealworm Tenebrio molitor. 20 mg of the dry pigment were resuspended in 10 mL of sterile 96% ethanol and subsequently filtered through a 0.20 μm sterile syringe filter. Various concentrations of the pigment were tested on both fourth instar larvae and adults of Tenebrio molitor using a leaf disk feeding assay. Disks measuring 5 cm in diameter were cut from cabbage leaves, dipped in the pigment concentrations, and allowed to dry for 30 min. Twenty larvae or adults were then placed in a Petri dish maintained at 25 °C and 60% relative humidity under a 12:12 h light-dark photoperiod for a duration of 5 days for each concentration.	A dose of 125 ppm of crude extract resulted in a 5% mortality rate, while a concentration of 2000 ppm caused a mortality rate of 68% in larvae and 30% in adults. The LC50 for the crude pigment in adults was found to be 4570 ppm. The mechanism of action was not specified.	[27]
Serratia marcescens KH-001. The bacterium was initially cultured in LB medium for 12 h at 28 °C and 180 rpm. Following this, a 2.5% inoculum was introduced into 50 mL of a basal medium, which contained 1.35 mg L−1 of olive oil, 500 mg L−1 of MgSO4, and 500 mg L−1 of beef extract, and fermentation was carried out for 48 h to produce prodigiosin. The mixture was then extracted using an equal volume of acetonitrile and sonicated for 30 min, after which NaCl was added. The supernatant was collected and concentrated in a rotary evaporator set at 55 °C. The crude product was harvested and stored at −80 °C. The crude product was purified by dissolving in a mixture of petroleum ether: ethyl acetate (3:1, v/v) and then passed through a column, followed by elution with the same solvent mixture.	Asian citrus psyllid Diaphorina citri Kuwayama. Toxicity assays were conducted at various temperatures with 10 mg of dried extracted pigment dissolved in 10 mL of methanol. Fresh citrus leaves were immersed in the resulting solutions for 10 s. After drying, each leaf was placed in a Petri dish containing ten fifth instar nymphs and then positioned in an illuminated incubator set to 25 °C, 30 °C, and 35 °C, with a relative humidity of 68 ± 2% and a light–dark photoperiod of 14:10 h. The impact on oviposition was assessed using one-year-old potted citrus plants sprayed with an aqueous solution of 40 mg L−1 prodigiosin. Two male and two female newly emerged adults (0–1 day old) were put into each cage for oviposition at 30 °C and 60% relative humidity, under a 14:10 h light–dark photoperiod for 7 days. Additionally, the influence of prodigiosin on egg hatching was evaluated using eggs that had not been exposed to pesticides. The leaves containing the eggs were soaked in a 40 mg L−1 prodigiosin aqueous solution for 10 s and then maintained in an illuminated incubator at 30 °C with a relative humidity of 68 ± 2% and a 14:10 h light–dark photoperiod for 4 days. Feeding impact was assessed with citrus leaves soaked in aqueous solutions of prodigiosin (12 and 40 mg L−1) for 30 s. Two leaf discs were placed into a Petri dish with a 1.5% agar solid medium at the bottom to secure them. Ten adult insects were released into each dish and maintained in an illuminated incubator at 30 °C and 68 ± 2% relative humidity with a 14:10 h light–dark photoperiods for 48 h.	At 30 °C, doses of prodigiosin at 12.64 and 40.53 mg L−1 resulted in mortalities of 50% (LC50) and 20% (LC20) of nymphs after 24 h, respectively. At 25 °C, the LC20 and LC50 values to D. citri were 40.09 and 223.79 mg L−1, respectively. At 35 °C, the LC20 and LC50 values for prodigiosin were 1.71 and 27.90 mg L−1, respectively. In experiments conducted at 30 °C using concentrations of 12 and 40 mg L−1, an oviposition inhibitory rate of 42% was observed, while egg hatching rates were found to be 65.30%. Additionally, adult feeding with 12 and 40 mg L−1 led to reductions in feeding of 28.02 and 34.66%, respectively. The mechanism of action was not specified.	[31]

summarizes multiple studies that confirm the prodigiosin’s efficacy against diverse insects, like species of mosquitoes (Aedes aegypti and Anopheles stephensi [26,29]), the Asian citrus psyllid Diaphorina citri [31], and various lepidopteran pests (Helicoverpa armigera, Spodoptera litura, Plutella xylostella [28,30]), among others [24,25,27].

A recurring observation is that larval stages are more susceptible than adults [26,27,29]. This heightened sensitivity could stem from morphological (thinner exoskeleton) and physiological (lower detoxification enzyme levels, reduced P-glycoprotein expression) factors [64]. The high efficacy against immature stages is advantageous as it curtails adult emergence and subsequent reproduction. Nonetheless, a study by Sree et al. reported complete adult mortality, suggesting that prodigiosin may be effective across multiple life stages [24]. Furthermore, prodigiosin can influence insect feeding and oviposition behaviour [31], broadening its potential use in integrated pest management programs.

5. Advantages and Limitations of the Use of Prodigiosin

Prodigiosin is a natural, eco-friendly pigment with documented insecticidal properties [65]. Its cytotoxic properties against epithelial cells indicate that prodigiosin is photostable, non-toxic, chemically inert, non-irritating, non-allergic, and non-carcinogenic [66]. Therefore, prodigiosin has significant potential as an insecticide. Conventional insect control methods, especially chemical substances, have many drawbacks. Many do not have specific biological activity, which can harm various life forms, affecting non-target organisms and presenting different hazard levels to humans, especially for pesticide applicators and farm workers. Also, these chemicals are often highly toxic to beneficial insects, like pollinators, natural predators, and parasites. In addition, target and non-target insects can develop resistance to these insecticides rapidly. The excessive dependence on chemical methods and lack of alternative control strategies keep agriculture from being in a more natural and balanced state [61]. Despite the advantages of prodigiosin, extracting it currently involves using toxic organic solvents. Therefore, developing methodologies for extracting and purifying prodigiosin using innocuous solvents is crucial.

Another challenge for the low bioavailability of prodigiosin is its high hydrophobic character (with an XLogP3-AA = 4.5) [5]. However, this issue can be addressed by combining prodigiosin with other compounds and materials. For instance, nanoparticles of zein–pectin were loaded with prodigiosin, previously prepared through electrostatic deposition and antisolvent precipitation methods. In this study, the authors achieved a zeta potential of −23.03 mV and a particle size of 184.13 nm, with an encapsulation efficiency of 89.05% and a loading capacity of 7.49% in the Z-Pet/PG 2:1 nanoparticle [67]. The low availability of prodigiosin can be overcome through different strategies, like nanocomposites. Nanocomposites are materials in which at least one of the phases shows dimensions in the nanometer range [68]. In a study, halloysite nanotubes have been combined with prodigiosin to increase bioavailability with medical applications [69]. On the other hand, bionanocomposites, also known as “green composites” or “bio-based plastics”, have some similarities with nanocomposites but important differences, like applications, functionalities, methods of preparation, compounds, properties, biodegradability, and biocompatibility. These compounds are made with a natural polymer and an inorganic compound at a nano-scale [1].

Another important aspect of prodigiosin is its primary producer species, Serratia marcescens, an opportunistic pathogen mainly affecting hospitalized and immunocompromised patients [70]. Fortunately, prodigiosin can also be produced by non-pathogenic strains, such as certain species from the genus Streptomyces. These species are recognized as potent producers of actinobacterial pigments and have applications in various industries due to their properties, including antioxidant and antimicrobial effects, immunosuppression, and antitumor activities [71]. One notable non-pathogenic species of Streptomyces that can produce prodigiosin is S. coelicolor, a key model organism and one of the first to be genetically and morphologically characterized [72]. For example, S. coelicolor A3 (2) was cultivated successfully, using a solid-state fermentation, achieving a prodigiosin production rate of 3.02 µM mL⁻¹ h⁻¹ [17]. This suggests that there is excellent potential for non-pathogenic species in the production of prodigiosin.

6. Conclusions

Insect pests threaten approximately 75% of major global crops, necessitating the development of more selective and eco-friendly control strategies. Prodigiosin—a tripyrrolic microbial pigment—emerges as a promising insecticide candidate due to its nontoxicity, environmental safety, and efficacy against multiple pest species and life stages. Nevertheless, most current production methods rely on Serratia marcescens, which is opportunistic and pathogenic. It is suggested that future efforts should emphasize using non-pathogenic strains like Streptomyces coelicolor and explore more sustainable extraction and purification methods.

The versatility of prodigiosin, from its biological activities to its potential synergistic formulations, highlights its value as an emerging bioinsecticide. Additional research involving field evaluations and formulation improvements will be key to establishing prodigiosin as a viable commercial solution within integrated pest management programmes. By addressing current limitations, prodigiosin could become a cornerstone in the shift toward safer, more sustainable agricultural practices.