Natural Bioactive Compounds from Macroalgae and Microalgae for the Treatment of Alzheimer's Disease: A Review.

Neuroinflammation, toxic protein aggregation, oxidative stress, and mitochondrial dysfunction are key pathways in neurodegenerative diseases like Alzheimer's disease (AD). Targeting these mechanisms with antioxidants, anti-inflammatory compounds, and inhibitors of Aß formation and aggregation is crucial for treatment. Marine algae are rich sources of bioactive compounds, including carbohydrates, phenolics, fatty acids, phycobiliproteins, carotenoids, fatty acids, and vitamins. In recent years, they have attracted interest from the pharmaceutical and nutraceutical industries due to their exceptional biological activities, which include anti-inflammation, antioxidant, anticancer, and anti-apoptosis properties. Multiple lines of evidence have unveiled the potential neuroprotective effects of these multifunctional algal compounds for application in treating and managing AD. This article will provide insight into the molecular mechanisms underlying the neuroprotective effects of bioactive compounds derived from algae based on in vitro and in vivo models of neuroinflammation and AD. We will also discuss their potential as disease-modifying and symptomatic treatment strategies for AD.

Seasonal environmental transitions and metabolic plasticity in a sea-ice alga from an individual cell perspective.

Sea-ice microalgae are a key source of energy and nutrient supply to polar marine food webs, particularly during spring, prior to open-water phytoplankton blooms. The nutritional quality of microalgae as a food source depends on their biomolecular (lipid:protein:carbohydrate) composition. In this study, we used synchrotron-based Fourier transform infra-red microspectroscopy (s-FTIR) to measure the biomolecular content of a dominant sea-ice taxa, Nitzschia frigida, from natural land-fast ice communities throughout the Arctic spring season. Repeated sampling over six weeks from an inner (relatively stable) and an outer (relatively dynamic) fjord site revealed high intra-specific variability in biomolecular content, elucidating the plasticity of N. frigida to adjust to the dynamic sea ice and water conditions. Environmental triggers indicating the end of productivity in the ice and onset of ice melt, including nitrogen limitation and increased water temperature, drove an increase in lipid and fatty acids stores, and a decline in protein and carbohydrate content. In the context of climate change and the predicted Atlantification of the Arctic, dynamic mixing and abrupt warmer water advection could truncate these important end-of-season environmental shifts, causing the algae to be released from the ice prior to adequate lipid storage, influencing carbon transfer through the polar marine system.

High biomass yields of Chlorella protinosa with efficient nitrogen removal from secondary effluent in a membrane photobioreactor.

Further treatment of secondary effluents before their discharge into the receiving water bodies could alleviate water eutrophication. In this study, the Chlorella proteinosa was cultured in a membrane photobioreactor to further remove nitrogen from the secondary effluents. The effect of hydraulic retention time (HRT) on microalgae biomass yields and nutrient removal was studied. The results showed that soluble algal products concentration reduced in the suspension at low HRT, thereby alleviating microalgal growth inhibition. In addition, the lower HRT reduced the nitrogen limitation for Chlorella proteinosa's growth through the phase-out of nitrogen-related functional bacteria. As a result, the productivity for Chlorella proteinosa increased from 6.12 mg/L/day at an HRT of 24 hr to 20.18 mg/L/day at an HRT of 8 hr. The highest removal rates of 19.7 mg/L/day, 23.8 mg/L/day, and 105.4 mg/L/day were achieved at an HRT of 8 hr for total nitrogen (TN), ammonia, and chemical oxygen demand (COD), respectively. However, in terms of removal rate, TN and COD were the largest when HRT is 24 hr, which were 74.5% and 82.6% respectively. The maximum removal rate of ammonia nitrogen was 99.2% when HRT was 8 hr.

Cell size, density, and nutrient dependency of unicellular algal gravitational sinking velocities.

Eukaryotic phytoplankton, also known as algae, form the basis of marine food webs and drive marine carbon sequestration. Algae must regulate their motility and gravitational sinking to balance access to light at the surface and nutrients in deeper layers. However, the regulation of gravitational sinking remains largely unknown, especially in motile species. Here, we quantify gravitational sinking velocities according to Stokes' law in diverse clades of unicellular marine microalgae to reveal the cell size, density, and nutrient dependency of sinking velocities. We identify a motile algal species, Tetraselmis sp., that sinks faster when starved due to a photosynthesis-driven accumulation of carbohydrates and a loss of intracellular water, both of which increase cell density. Moreover, the regulation of cell sinking velocities is connected to proliferation and can respond to multiple nutrients. Overall, our work elucidates how cell size and density respond to environmental conditions to drive the vertical migration of motile algae.

Microalgae-mediated bioremediation: current trends and opportunities-a review.

Environmental pollution poses a critical global challenge, and traditional wastewater treatment methods often prove inadequate in addressing the complexity and scale of this issue. On the other hand, microalgae exhibit diverse metabolic capabilities that enable them to remediate a wide range of pollutants, including heavy metals, organic contaminants, and excess nutrients. By leveraging the unique metabolic pathways of microalgae, innovative strategies can be developed to effectively remediate polluted environments. Therefore, this review paper highlights the potential of microalgae-mediated bioremediation as a sustainable and cost-effective alternative to conventional methods. It also highlights the advantages of utilizing microalgae and algae-bacteria co-cultures for large-scale bioremediation applications, demonstrating impressive biomass production rates and enhanced pollutant removal efficiency. The promising potential of microalgae-mediated bioremediation is emphasized, presenting a viable and innovative alternative to traditional treatment methods in addressing the global challenge of environmental pollution. This review identifies the opportunities and challenges for microalgae-based technology and proposed suggestions for future studies to tackle challenges. The findings of this review advance our understanding of the potential of microalgae-based technology wastewater treatment.

Performance of four different microalgae-based technologies in antibiotics removal under multiple concentrations of antibiotics and strigolactone analogue GR24 administration.

The formation of symbionts by using different combinations of endophytic bacteria, microalgae, and fungi to purify antibiotics-containing wastewater is an effective and promising biomaterial technology. As it enhances the mixed antibiotics removal performance of the bio-system, this technology is currently extensively studied. Using exogenous supplementation of various low concentrations of the phytohormone strigolactone analogue GR24, the removal of various antibiotics from simulated wastewater was examined. The performances of Chlorella vulgaris monoculture, activated sludge-C. vulgaris-Clonostachys rosea, Bacillus licheniformis-C. vulgaris-C. rosea, and endophytic bacteria (S395-2)-C. vulgaris-C. rosea co-culture systems were systematically compared. Their removal capacities for tetracycline, oxytetracycline, and chlortetracycline antibiotics from simulated wastewater were assessed. Chlorella vulgaris-endophytic bacteria-C. rosea co-cultures achieved the best performance under 0.25 mg L-1 antibiotics, which could be further enhanced by GR24 supplementation. This result demonstrates that the combination of endophytic bacteria with microalgae and fungi is superior to activated sludge-B. licheniformis-microalgae-fungi systems. Exogenous supplementation of GR24 is an effective strategy to improve the performance of antibiotics removal from wastewater.

The Microalgae Chlamydomonas for Bioremediation and Bioproduct Production.

The extensive metabolic diversity of microalgae, coupled with their rapid growth rates and cost-effective production, position these organisms as highly promising resources for a wide range of biotechnological applications. These characteristics allow microalgae to address crucial needs in the agricultural, medical, and industrial sectors. Microalgae are proving to be valuable in various fields, including the remediation of diverse wastewater types, the production of biofuels and biofertilizers, and the extraction of various products from their biomass. For decades, the microalga Chlamydomonas has been widely used as a fundamental research model organism in various areas such as photosynthesis, respiration, sulfur and phosphorus metabolism, nitrogen metabolism, and flagella synthesis, among others. However, in recent years, the potential of Chlamydomonas as a biotechnological tool for bioremediation, biofertilization, biomass, and bioproducts production has been increasingly recognized. Bioremediation of wastewater using Chlamydomonas presents significant potential for sustainable reduction in contaminants and facilitates resource recovery and valorization of microalgal biomass, offering important economic benefits. Chlamydomonas has also established itself as a platform for the production of a wide variety of biotechnologically interesting products, such as different types of biofuels, and high-value-added products. The aim of this review is to achieve a comprehensive understanding of the potential of Chlamydomonas in these aspects, and to explore their interrelationship, which would offer significant environmental and biotechnological advantages.

ROS and Ca2+ signaling involved in important lipid changes of Chlorella pyrenoidosa under nitrogen stress conditions.

MAIN CONCLUSION: Nitrogen stress altered important lipid parameters and related genes in Chlorella pyrenoidosa via ROS and Ca2+ signaling. The mutual interference between ROS and Ca2+ signaling was also uncovered. The changed mechanisms of lipid parameters (especially lipid classes and unsaturation of fatty acids) in microalgae are not completely well known under nitrogen stress. Therefore, Chlorella pyrenoidosa was exposed to 0, 0.5, 1 and 1.5 g L-1 NaNO3 for 4 days. Then, the physiological and biochemical changes were measured. It was shown that the total lipid contents, neutral lipid ratios as well as their related genes (accD and DGAT) increased obviously while the polar lipid ratios, degrees of unsaturation as well as their related genes (PGP and desC) decreased significantly in nitrogen stress groups. The obvious correlations supported that gene expressions should be the necessary pathways to regulate the lipid changes in C. pyrenoidosa under nitrogen stress. The changes in ROS and Ca2+ signaling as well as their significant correlations with corresponding genes and lipid parameters were analyzed. The results suggested that ROS and Ca2+ may regulate these gene expressions and lipid changes in C. pyrenoidosa under nitrogen stress conditions. This was verified by the subordinate tests with an ROS inhibitor and calcium reagents. It also uncovered the clues of mutual interference between ROS and Ca2+ signaling. To summarize, this study revealed the signaling pathways of important lipid changes in microalgae under N stress.

Microalgae protein digestibility: How to crack open the black box?

Microalgae are booming as a sustainable protein source for human nutrition and animal feed. Nevertheless, certain strains were reported to have robust cell walls limiting protein digestibility. There are several disruption approaches to break down the cell integrity and increase digestive enzyme accessibility. This review's intent is to discuss the digestibility of microalgae proteins in intact cells and after their disruption. In intact single cells, the extent of protein digestibility is chiefly related to cell wall structural properties (differing among strains) as well as digestion method and when added to food or feed protein digestibility changes depending on the matrix's composition. The degree of effectiveness of the disruption method varies among studies, and it is complicated to compare them due to variabilities in digestibility models, strains, disruption method/conditions and their consequent impact on the microalgae cell structure. More exhaustive studies are still required to fill knowledge gaps on the structure of microalgal cell walls and to find efficient and cost-effective disruption technologies to increase proteins availability without hindering their quality.

Biomining using microalgae to recover rare earth elements (REEs) from bauxite.

Biomining using microalgae has emerged as a sustainable option to extract rare earth elements (REEs). This study aims to (i) explore the capability of REEs recovery from bauxite by microalgae, (ii) assess the change of biochemical function affected by bauxite, and (iii) investigate the effects of operating conditions (i.e., aeration rate, pH, hydraulic retention time) to REEs recovery. The results showed that increasing bauxite in microalgae culture increases REEs recovery in biomass and production of biochemical compounds (e.g., pigments and Ca-Mg ATPase enzyme) up to 10 %. The optimum pulp ratio of bauxite in the microalgae culture ranges from 0.2 % to 0.6 %. Chlorella vulgaris was the most promising, with two times higher in REEs recovery in biomass than the other species. REEs accumulated in microalgae biomass decreased with increasing pH in the culture. This study establishes a platform to make the scaling up of REEs biomining by microalgae plausible.

Traditional and new trend strategies to enhance pigment contents in microalgae.

Microalgae are a source of a wide variety of commodities, including particularly valuable pigments. The typical pigments present in microalgae are the chlorophylls, carotenoids, and phycobiliproteins. However, other types of pigments, of the family of water-soluble polyphenols, usually encountered in terrestrial plants, have been recently reported in microalgae. Among such microalgal polyphenols, many flavonoids have a yellowish hue, and are used as natural textile dyes. Besides being used as natural colorants, for example in the food or cosmetic industry, microalgal pigments also possess many bioactive properties, making them functional as nutraceutical or pharmaceutical agents. Each type of pigment, with its own chemical structure, fulfills particular biological functions. Considering both eukaryotes and prokaryotes, some species within the four most promising microalgae groups (Cyanobacteria, Rhodophyta, Chlorophyta and Heterokontophyta) are distinguished by their high contents of specific added-value pigments. To further enhance microalgae pigment contents during autotrophic cultivation, a review is made of the main related strategies adopted during the last decade, including light adjustments (quantity and quality, and the duration of the photoperiod cycle), and regard to mineral medium characteristics (salinity, nutrients concentrations, presence of inductive chemicals). In contrast to what is usually observed for growth-related pigments, accumulation of non-photosynthetic pigments (polyphenols and secondary carotenoids) requires particularly stressful conditions. Finally, pigment enrichment is also made possible with two new cutting-edge technologies, via the application of metallic nanoparticles or magnetic fields.

Engineered Chlorella vulgaris improves bioethanol production and promises prebiotic application.

Microalgal biomass for biofuel production, integration into functional food, and feed supplementation has generated substantial interest worldwide due to its high growth rate, non-competitiveness for agronomic land, ease of cultivation in containments, and presence of several bioactive molecules. In this study, genetic engineering tools were employed to develop transgenic lines of freshwater microalga Chlorella vulgaris with a higher starch content, by up-regulating ADP-glucose pyrophosphorylase (AGPase), which is a rate-limiting enzyme in starch biosynthesis. Expression of the Escherichia coli glgC (AGPase homolog) gene in C. vulgaris led to an increase in total carbohydrate content up to 45.1% (dry cell weight, DCW) in the transgenic line as compared to 34.2% (DCW) in the untransformed control. The starch content improved up to 16% (DCW) in the transgenic alga compared to 10% (DCW) in the control. However, the content of total lipid, carotenoid, and chlorophyll decreased differentially in the transgenic lines. The carbohydrate-rich biomass from the transgenic algal line was used to produce bioethanol via yeast fermentation, which resulted in a higher ethanol yield of 82.82 mg/L as compared to 54.41 mg/L from the untransformed control. The in vitro digestibility of the transgenic algal starch revealed a resistant starch content of up to 7% of total starch. Faster growth of four probiotic bacterial species along with a lowering of the pH of the growth medium indicated transgenic alga to exert a positive prebiotic effect. Taken together, the study documents the utilization of genetically engineered C. vulgaris with enriched carbohydrates as bioethanol feedstock and functional food ingredients.

High-Throughput Metabolite Analysis of Unicellular Microalgae by Orthogonal Hybrid Ionization Label-Free Mass Cytometry.

Microalgae metabolite analysis is fundamental for the rational design of metabolic engineering strategies for the biosynthesis of high-value products. Mass spectrometry (MS) has been utilized for single-cell microalgae analysis. However, limitations in the detection throughput and polarities of detectable substances make it difficult to realize high-throughput screening of high-performance microalgae. Herein, a plasma-assisted label-free mass cytometry, named as PACyESI-MS, was proposed combining the advantages of orthogonal hybrid ionization and high-throughput MS analysis, which realized rapid metabolite detection of single microalgae. The cell detection throughput of PACyESI-MS was up to 52 cells/min. Dozens of the critical primary and secondary metabolites within single microalgae were detected simultaneously, including pigments, lipids, and energy metabolites. Furthermore, metabolite changes of Chlamydomonas reinhardtii and Haematococcus pluvialis under nitrogen deficiency stress were studied. Discrimination of Chlamydomonas under different nutrient conditions was realized using single-cell metabolite profiles obtained by PACyESI-MS. The relationships between the accumulation of bioactive astaxanthin and changes in functional primary metabolites of Haematococcus were investigated. It was demonstrated that PACyESI-MS can detect the flexible change of metabolites in single microalgae cells under different nutritional conditions and during the synthesis of high-value products, which is expected to become an important tool for the design of metabolic engineering-based high-performance microalgae factories.

Optimal conditions of algal breeding using neutral beam and applying it to breed Euglena gracilis strains with improved lipid accumulation.

Microalgae are considered to be more useful and effective to use in biomass production than other photosynthesis organisms. However, microalgae need to be altered to acquire more desirable traits for the relevant purpose. Although neutron radiation is known to induce DNA mutations, there have been few studies on its application to microalgae, and the optimal relationship between irradiation intensity and mutation occurrence has not been established. In this study, using the unicellular red alga Cyanidioschyzon merolae as a model, we analyzed the relationship between the absorbed dose of two types of neutrons, high-energy (above 1 MeV) and thermal (around 25 meV) neutrons, and mutation occurrence while monitoring mutations in URA5.3 gene encoding UMP synthase. As a result, the highest mutational occurrence was observed when the cells were irradiated with 20 Gy of high-energy neutrons and 13 Gy of thermal neutrons. Using these optimal neutron irradiation conditions, we next attempted to improve the lipid accumulation of Euglena gracilis, which is a candidate strain for biofuel feedstock production. As a result, we obtained several strains with a maximum 1.3-fold increase in lipid accumulation compared with the wild-type. These results indicate that microalgae breeding by neutron irradiation is effective.

The Role of PGPB-Microalgae interaction in Alleviating Salt Stress in Plants.

Plant development and yield are severely hampered by climate change. Plants are very prone to a variety of abiotic stressors during growth, making them susceptible to destruction which can reduce the productivity by 20-60%. These stresses generate reactive oxygen species (ROS), which damage lipids, proteins, and nucleic acids. Microalgae and plant growth-promoting bacteria (PGPB) are remarkably effective at reducing the effects of salt stress and promoting plant growth, thereby increasing agricultural yield, and helping ensure global food security. Through a variety of mechanisms, including the production of phytohormones, 1-aminocyclopropane-1-carboxylic acid deaminase, exopolysaccharide, siderophores, hydrogen cyanide, extracellular polymeric substances, volatile organic compounds, and modulation of antioxidants defense machinery under abiotic stresses promote plant growth after inoculation of PGPB and microalgae. These microorganisms also maintain ion homeostasis, offer osmotic balance, stimulate genes that respond to salt and drought, rewire the metabolism, modify the transcription of ion transporter genes, and more. To counteract the negative consequences of salinity stress, this study summarizes the effects of PGPB- microalgae along with a tentative protective mechanism during salinity stress for sustainable agriculture.

Bioremediation potential of microalgae for sustainable soil treatment in India: A comprehensive review on heavy metal and pesticide contaminant removal.

The escalating environmental concerns arising from soils contamination with heavy metals (HMs) and pesticides (PSTs) necessitate the development of sustainable and effective remediation strategies. These contaminants, known for their carcinogenic properties and toxicity even at small amounts, pose significant threats to both environmental ecology and human health. While various chemical and physical treatments are employed globally, their acceptance is often hindered by prolonged remediation times, high costs, and inefficacy in areas with exceptionally high pollutant concentrations. A promising emerging trend in addressing this issue is the utilization of microalgae for bioremediation. Bioremediation, particularly through microalgae, presents numerous benefits such as high efficiency, low cost, easy accessibility and an eco-friendly nature. This approach has gained widespread use in remediating HM and PST pollution, especially in large areas. This comprehensive review systematically explores the bioremediation potential of microalgae, shedding light on their application in mitigating soil pollutants. The paper summarizes the mechanisms by which microalgae remediate HMs and PSTs and considers various factors influencing the process, such as pH, temperature, pollutant concentration, co-existing pollutants, time of exposure, nutrient availability, and light intensity. Additionally, the review delves into the response and tolerance of various microalgae strains to these contaminants, along with their bioaccumulation capabilities. Challenges and future prospects in the microalgal bioremediation of pollutants are also discussed. Overall, the aim is to offer valuable insights to facilitate the future development of commercially viable and efficient microalgae-based solutions for pollutant bioremediation.

The enzyme encoded by Myrmecia incisa, a green microalga, phospholipase A2 gene preferentially hydrolyzes arachidonic acid at the sn-2 position of phosphatidylcholine.

The enzyme phospholipase A2 (PLA2) plays a crucial role in acyl remodeling of phospholipids via the Lands' cycle, and consequently alters fatty acid compositions in triacylglycerol (TAG). In this study, a full-length cDNA sequence coding Myrmecia incisa phospholipase A2 (MiPLA2) was cloned using the technique of rapid amplification of cDNA ends. Comparison of the 1082-bp cDNA with its corresponding cloned DNA sequence revealed that MiPLA2 contained 3 introns. Mature MiPLA2 (mMiPLA2) had a conserved Ca2+-binding loop and a catalytic site motif that has been recognized in plant secretory PLA2 (sPLA2) proteins. Correspondingly, phylogenetic analysis illustrated that MiPLA2 was clustered within GroupXIA of plant sPLA2 proteins. To ascertain the function of MiPLA2, the cDNA coding for mMiPLA2 was subcloned into the vector pET-32a to facilitate the production of recombinant mMiPLA2 in Escherichia coli. Recombinant mMiPLA2 was purified and used for the in vitro enzyme reaction. Thin-layer chromatography profiles of the catalytic products generated by recombinant mMiPLA2 indicated a specificity for cleaving sn-2 acyl chains from phospholipids, thereby functionally characterizing MiPLA2. Although recombinant mMiPLA2 displayed a strong preference for phosphatidylethanolamine, it preferentially hydrolyzes arachidonic acid (ArA) at the sn-2 position of phosphatidylcholine. Results from the fused expression of p1300-sp-EGFP-mMiPLA2 illustrated that MiPLA2 was localized in the intercellular space of onion epidermis. Furthermore, the positive correlation between MiPLA2 transcription and free ArA levels were established. Consequently, the role of mMiPLA2 in the biosynthesis of ArA-rich TAG was elucidated. This study helps to understand how M. incisa preferentially uses ArA to synthesize TAG.

Enhancement of biomass productivity and biochemical composition of alkaliphilic microalgae by mixotrophic cultivation using cheese whey for biofuel production.

The growth of microalgae under alkaline conditions ensures an ample supply of CO2 from the atmosphere, with a low risk of crashing due to contamination and predators. The present study investigated the mixotrophic cultivation of two alkaliphilic microalgae (Tetradesmus obliquus and Cyanothece sp.) using cheese whey as an organic carbon source. The variation in cheese whey concentration (0.5-4.5% (v/v)), culture pH (7-11), and NaNO3 concentrations (0-2 gL-1) was evaluated using central composite design in response to biomass productivity and the contents of lipids, total proteins, and soluble carbohydrates. Both investigated microalgae effectively utilized cheese whey as an organic carbon source. The optimum conditions for simultaneously maximizing biomass and lipid productivity in T. obliquus were 3.5% (v/v) whey, pH 10.0, and 0.5 g L-1 NaNO3. Under these conditions, the biomass, lipid, soluble carbohydrate, and protein productivities were 48.69, 20.64, 7.02, and 10.97 mg L-1 day-1, respectively. Meanwhile, Cyanothece produced 52.78, 11.42, 4.31, and 7.89 mg L-1 day-1 of biomass, lipid, carbohydrate, and protein, respectively, at 4.5% (v/v) whey, pH 9.0, and 1.0 g L-1 NaNO3. The lipids produced under these conditions were rich in saturated fatty acids (FAs) and monounsaturated FAs, with no polyunsaturated FAs in both microalgae. Moreover, several biodiesel characteristics were estimated, and results fell within the ranges specified by international standards. These findings indicate that the mixotrophic cultivation of alkaliphilic microalgae could open new avenues for promoting microalgae productivity through low-cost biofuel production.

Distribution and Level of Bioactive Monoacylglycerols in 12 Marine Microalgal Species.

Microalgae are currently considered an attractive source of highly valuable metabolites potentially exploitable as anticancer agents, nutraceuticals and cosmeceuticals and for bioenergy purposes. Their ease of culturing and their high growth rates further promote their use as raw material for the production of specialty products. In the present paper, we focused our attention on specific glycerol-based lipid compounds, monoacylglycerols (MAGs), which displayed in our previous studies a selective cytotoxic activity against the haematological U-937 and the colon HCT-116 cancer cell lines. Here, we performed a quali/quantitative analysis of MAGs and total fatty acids (FAs) along with a profiling of the main lipid classes in a panel of 12 microalgal species, including diatoms and dinoflagellates. Our results highlight an inter- and intraspecific variability of MAG profile in the selected strains. Among them, Skeletonema marinoi (strain FE7) has emerged as the most promising source for possible biotechnological production of MAGs.

Pharmaceutical removal from wastewater by introducing cytochrome P450s into microalgae.

Pharmaceuticals are of increasing environmental concern as they emerge and accumulate in surface- and groundwater systems around the world, endangering the overall health of aquatic ecosystems. Municipal wastewater discharge is a significant vector for pharmaceuticals and their metabolites to enter surface waters as humans incompletely absorb prescription drugs and excrete up to 50% into wastewater, which are subsequently incompletely removed during wastewater treatment. Microalgae present a promising target for improving wastewater treatment due to their ability to remove some pollutants efficiently. However, their inherent metabolic pathways limit their capacity to degrade more recalcitrant organic compounds such as pharmaceuticals. The human liver employs enzymes to break down and absorb drugs, and these enzymes are extensively researched during drug development, meaning the cytochrome P450 enzymes responsible for metabolizing each approved drug are well studied. Thus, unlocking or increasing cytochrome P450 expression in endogenous wastewater microalgae could be a cost-effective strategy to reduce pharmaceutical loads in effluents. Here, we discuss the challenges and opportunities associated with introducing cytochrome P450 enzymes into microalgae. We anticipate that cytochrome P450-engineered microalgae can serve as a new drug removal method and a sustainable solution that can upgrade wastewater treatment facilities to function as "mega livers".