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A special issue of Marine Drugs (ISSN 1660-3397). This special issue belongs to the section "Marine Biotechnology Related to Drug Discovery or Production".

Deadline for manuscript submissions: 31 May 2026 | Viewed by 14384

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Special Issue Editor

Dr. Yi Xin

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Guest Editor

School of Marine Biology and Fisheries, Hainan University, Haikou, China
Interests: microalgae; lipid metabolism; synthetic biology; metabolic engineering
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Dear Colleagues,

Marine microalgae are attracting renewed interest from both the scientific and public communities, owing to their potential applications as sustainable feed stock for the production of biofuels and high-value compounds. Compared with traditional crops, marine microalgae have the advantages of rapid growth, high lipid content, the non-occupation of arable land, etc. Therefore, marine microalgae are considered to be ideal chassis for the high production of endogenous or heterogenous compounds. Synthetic biology has emerged as a powerful tool for engineering biological systems to produce valuable compounds, including pharmaceuticals and nutraceuticals. Marine microalgae, in particular, endow a promising platform for the production of bioactive compounds, due to considerable omics data and efficient toolkits for genetic engineering. The present Special Issue, edited by Dr. Yi Xin, will focus on resources, products, technologies, and approaches for synthetic biology in marine microalgae.

Dr. Yi Xin
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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Keywords

marine microalgae
high-value compounds
biomass
photosynthesis
synthetic biology
function modules
genetic engineering
metabolic engineering
conditional expression
stress response

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Published Papers (6 papers)

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Research

Jump to: Review

21 pages, 3786 KB

Open AccessArticle

Enhanced Synechococcus Growth Under Extended High-Light and High-Temperature Stress by the F₁-α-C252Y Mutation in ATP Synthase: ATP Generation and Metabolic Network Remodeling

by Linan Zhou, Wenjing Lou, Xin Guo, Siyan Yi, Wenhui Lou, Guodong Luan and Xuefeng Lu

Mar. Drugs 2026, 24(5), 152; https://doi.org/10.3390/md24050152 - 25 Apr 2026

Viewed by 1141

Abstract

Photosynthesis, the main energy source for life on Earth, confronts escalating challenges of high-light–high-temperature stress (HLHT). Our previous study identified a mutation in ATP synthase, F₁-α-C252Y, that significantly enhances the HLHT tolerance of Synechococcus elongatus PCC 7942 (Sye7942), although the underlying mechanism remains obscure. In this study, we found that this mutation led to elevated levels of the b subunit of F_o, F₁ subunits, and the ATP synthase within cells, without affecting ATP synthetic activity, indicating improved intracellular ATP synthesis activity. Additionally, the mutation altered the transcriptome of Sye7942, impacting the expression of genes involved in crucial processes, such as the electron transport chain, carbon fixation, and regulatory factors, which are crucial for cyanobacteria’s adaptation to stresses. Correspondingly, the mutant exhibited enhanced photosynthesis, accelerated growth, and increased glycogen under HLHT conditions, showing improved adaptation. The higher intracellular ATP synthesis activity, along with enhanced photosynthetic activity, suggests increased ATP production in the mutant under HLHT. Enhancing ATP production and remodeling the cellular transcriptome appear to be key strategies employed by the C252Y mutation for Sye7942 acclimating to HLHT. These findings provide valuable insights for enhancing photosynthetic efficiency and stress resilience in cyanobacteria and other photosynthetic organisms facing HLHT challenges. Full article

(This article belongs to the Special Issue Synthetic Biology in Marine Microalgae)

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13 pages, 4145 KB

Open AccessArticle

Enhanced DHA Production in Aurantiochytrium by ω-3 Desaturase Integration and Fatty Acid Synthase Disruption

by Ziyu Wang, Yujian Wang, Weijian Wan, Chao Chen, Wen Wen, Xiaojin Song, Jinsong Xuan and Yingang Feng

Mar. Drugs 2026, 24(4), 144; https://doi.org/10.3390/md24040144 - 20 Apr 2026

Cited by 1 | Viewed by 861

Abstract

Docosahexaenoic acid (DHA) is an essential ω-3 polyunsaturated fatty acid (PUFA) with high nutritional and pharmaceutical value. The marine protist Aurantiochytrium is a promising industrial DHA producer; however, its DHA biosynthesis via the PUFA synthase pathway co-produces ω-6 docosapentaenoic acid (DPA), limiting DHA purity. Here, we introduced an ω-3 desaturase from Phytophthora infestans (Pin-O3D) into Aurantiochytrium sp. SD116. Functional validation in an Escherichia coli system co-expressing the native PUFA synthase confirmed that Pin-O3D converts DPA to DHA, shifting the DHA/DPA ratio from 1:1 to 2:1. Pin-O3D was then integrated into the fatty acid synthase (FAS) locus, simultaneously attenuating FAS activity and enabling heterologous gene expression. The engineered strain ΔFAS-Pin-O3D exhibited significantly (p < 0.0001 in t-test) increased DHA content (55.2% of total fatty acids) and DHA/DPA ratio (5.91) in shake flasks, with no negative impact on biomass or lipid accumulation. Fed-batch fermentation confirmed the scalability of this strategy, achieving a >20% increase in DHA/DPA ratio. This study demonstrates that combining heterologous ω-3 desaturase expression with FAS attenuation is an effective approach for optimizing PUFA profiles in Aurantiochytrium. Full article

(This article belongs to the Special Issue Synthetic Biology in Marine Microalgae)

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17 pages, 1811 KB

Open AccessArticle

Harnessing Biogas into High-Value Chemicals: The Role of Algal–Methanotrophic Co-Cultures

by Rebecca Serna-García, Ysis Lanzoni, Octavio García-Depraect, Raul Muñoz and Sara Cantera

Mar. Drugs 2026, 24(2), 81; https://doi.org/10.3390/md24020081 - 17 Feb 2026

Viewed by 1294

Abstract

The conversion of biogas into high-value chemicals for pharmaceutical, cosmetic, and nutraceutical markets offers an attractive alternative to conventional fossil-based production routes, enabling circular value chains with significant socio-economic impact. This study evaluated the valorization of biogas into osmolyte and carotenoid compounds with market prices ranging from 1000 to 7000 $·kg⁻¹. Specifically, an algal–methanotrophic co-culture operated under saline conditions, preventing external microbial contamination and stimulating osmolytes and carotenoids, was assessed for its capacity to simultaneously remove methane (CH₄) and carbon dioxide (CO₂), with efficiencies of 92 and 89%, respectively. while producing ectoine, hydroxyectoine, lutein, β-carotene, and astaxanthin. Shotgun metagenomic analyses identified the key microorganisms driving the process, predominantly alkaliphilic and halophilic green algae (Chlorella, Dunaliella) and cyanobacteria (Leptolyngbya), and halotolerant methanotrophs (Methylotuvimicrobium) and methylotrophs (Methylophaga). Metagenomics further revealed the presence of key metabolisms related to C1 utilization and biosynthetic genes associated with carotenoid and osmolyte production, confirming the metabolic potential of the consortium to convert biogas-derived carbon directly into high-value compounds. Overall, these results demonstrate the feasibility of an efficient, biologically driven bio-platform capable of transforming greenhouse gas-rich waste streams into economically relevant bioactive molecules, contributing to global priorities in sustainable biomass-to-biochemical innovation. Full article

(This article belongs to the Special Issue Synthetic Biology in Marine Microalgae)

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28 pages, 7480 KB

Open AccessArticle

Effect of Heterologous Expression of Key Enzymes Involved in Astaxanthin and Lipid Synthesis on Lipid and Carotenoid Production in Aurantiochytrium sp.

by Yaping Shao, Zhengquan Gao, Fengjie Sun, Yulin Cui, Xinyu Zou, Jinju Ma, Qiaolei Wang, Hao Zhang, Yuyong Wu and Chunxiao Meng

Mar. Drugs 2025, 23(4), 164; https://doi.org/10.3390/md23040164 - 11 Apr 2025

Cited by 2 | Viewed by 3182

Abstract

Aurantiochytrium sp., a heterotrophic microorganism, has received increasing attention for its high production of polyunsaturated fatty acids and has been widely applied in various industries. This study intended to optimize the carotenoid synthesis pathway in Aurantiochytrium sp. by metabolic engineering to increase the carotenoid content. Multi-sourced key enzyme genes involved in lipid synthesis (LPAAT and DGAT) and astaxanthin synthesis (crtZ and crtW) were selected to construct single-gene expression vectors and transformed into Aurantiochytrium sp. The results showed that the overexpression of LPAAT of Phaeodactylum tricornutum in Aurantiochytrium sp. caused an increase of 39.3% in astaxanthin, 424.7% in β-carotene, 901.8% in canthaxanthin, and 575.9% in lutein, as well as a down-regulation of 15.3% in the fatty acid content. Transcriptomics analysis revealed enhanced expression of genes involved in purine and amino acid metabolism in the transformed strains, and the down-regulation of the citric acid cycle led to an increase in the source of acetyl coenzyme A for the production of fatty acids. This study provides strong experimental evidence to support the application of increasing carotenoid levels in Aurantiochytrium sp. Full article

(This article belongs to the Special Issue Synthetic Biology in Marine Microalgae)

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15 pages, 5680 KB

Open AccessArticle

Enhanced Eicosapentaenoic Acid Production via Synthetic Biological Strategy in Nannochloropsis oceanica

by Congcong Miao, Mingting Du, Hongchao Du, Tao Xu, Shan Wu, Xingwei Huang, Xitao Chen, Suxiang Lei and Yi Xin

Mar. Drugs 2024, 22(12), 570; https://doi.org/10.3390/md22120570 - 19 Dec 2024

Cited by 10 | Viewed by 2811

Abstract

The rational dietary ratio of docosahexaenoic acid (DHA) to eicosapentaenoic acid (EPA) can exert neurotrophic and cardiotrophic effects on the human body. The marine microalga Nannochloropsis oceanica produces EPA yet no DHA, and thus, it is considered an ideal EPA-only model to pursue a rational DHA/EPA ratio. In this study, synthetic biological strategy was applied to improve EPA production in N. oceanica. Firstly, to identify promoters and terminators, fifteen genes from N. oceanica were isolated using a transcriptomic approach. Compared to α-tubulin, NO08G03500, NO03G03480 and NO22G01450 exhibited 1.2~1.3-fold increases in transcription levels. Secondly, to identify EPA-synthesizing modules, putative desaturases (NoFADs) and elongases (NoFAEs) were overexpressed by the NO08G03500 and NO03G03480 promoters/terminators in N. oceanica. Compared to the wild type (WT), NoFAD1770 and NoFAE0510 overexpression resulted in 47.7% and 40.6% increases in EPA yields, respectively. Thirdly, to store EPA in triacylglycerol (TAG), NoDGAT2K was overexpressed using the NO22G01450 promoter/terminator, along with NoFAD1770–NoFAE0510 stacking, forming transgenic line XS521. Compared to WT, TAG-EPA content increased by 154.8% in XS521. Finally, to inhibit TAG-EPA degradation, a TAG lipase-encoding gene NoTGL1990 was knocked out in XS521, leading to a 49.2–65.3% increase in TAG-EPA content. Our work expands upon EPA-enhancing approaches through synthetic biology in microalgae and potentially crops. Full article

(This article belongs to the Special Issue Synthetic Biology in Marine Microalgae)

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Review

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25 pages, 3740 KB

Open AccessReview

Microalgae-Based 3D Bioprinting: Recent Advances, Applications and Perspectives

by Jinhui Tang, Jiahui Sun, Jinyu Cui, Xiangyi Yuan, Guodong Luan and Xuefeng Lu

Mar. Drugs 2025, 23(9), 342; https://doi.org/10.3390/md23090342 - 27 Aug 2025

Cited by 3 | Viewed by 3815

Abstract

Three-dimensional bioprinting integrating living cells and bioactive materials enables the fabrication of scaffold structures supporting diverse cellular growth and metabolism. Microalgae are among the most promising microbial platforms for the construction of photosynthetic cell factories, while the current industrial-scale cultivation of microalgae remains predominantly dependent on traditional liquid submerged systems, imposing limitations on commercial viability due to both process and economic constraints. Encapsulation of microalgae within bioactive matrices combined with 3D bioprinting to fabricate customized structures has been explored to address the limitations of submerged cultivation, which are expected to expand microalgal applications and establish new research directions in microalgal biotechnology. This review analyzes both matrices and methods of 3D bioprinting, summarizing the advancement of microalgae-based 3D bioprinting into six main domains including living building materials, biophotovoltaics, photosynthetic biosynthesis, bioremediation, tissue engineering, and food engineering. Lastly, synthetic biology-informed perspectives are provided on future developments of 3D bioprinting technologies and their potential in microalgal research. Full article

(This article belongs to the Special Issue Synthetic Biology in Marine Microalgae)

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