Synthetic Biology and Engineering

Guide for Authors Submit to SBE

Issue 4, Volume 3 – 5 articles

Cover Story (View full-size image):
Human milk oligosaccharides (HMOs), the third most abundant solid component in human milk after lactose and lipids, are recognized as crucial prebiotics that support infant gut health and immune development. Salivary HMOs account for approximately 13% of the total HMOs molar ratio, with 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL) accounting for approximately 2% and 6%, respectively. Sialyllactose (SL) exhibits a range of notable physiological functions, including prebiotic activity, antiviral properties, prevention of necrotizing enterocolitis, immunomodulatory effects, and enhancement of brain development and cognition. Both 3′-SL and 6′-SL have been approved as “Generally Recognized as Safe” (GRAS) by the U.S. FDA and are increasingly incorporated into infant formula. Currently, the biosynthesis of SL is mainly efficiently produced through engineered microorganisms. However, face bottlenecks: low yields, complex downstream processing, and prohibitive costs. Recent advances in synthetic biology and metabolic engineering offer promising avenues to overcome these barriers. This review introduces the synthesis methods, functions, and applications of SL, as well as conducting safety evaluation and regulatory status analysis. We hope this article will enhance understanding of the challenges encountered in the synthetic biology production and application of SL.
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Open Access

Review

04 November 2025

Tools and Strategies for Engineering Bacillus methanolicus: A Versatile Thermophilic Platform for Sustainable Bioproduction from Methanol and Alternative Feedstocks

Bacillus methanolicus MGA3 is a methylotrophic bacterium with a high potential as a production host in the bioeconomy, particularly with methanol as a feedstock. This review presents the recent acceleration in strain engineering technologies through advances in transformation efficiency, the development of CRISPR/Cas9-based genome editing, and the application of genome-scale models (GSMs) for strain design. The generation of novel genetic tools broadens the biotechnological potential of this thermophilic methylotroph. B. methanolicus is a facultative methylotroph and apart from methanol it can grow on mannitol, arabitol and glucose, and was engineered for starch and xylose utilisation. Here, the central carbon metabolism of B. methanolicus for various native and non-native carbon sources is described, with an emphasis on methanol metabolism. With its expanding product portfolio, B. methanolicus demonstrates its potential as a microbial cell factory for the production of tricarboxylic acid(TCA) cycle and ribulose monophosphate (RuMP) cycle intermediates and their derivatives. Beyond small chemicals, B. methanolicus is both a valuable source of novel thermostable proteins and a host for the production of heterologous proteins, enabled by advances in genetic tools and cultivation methods. Continued progress in understanding its physiology and refining its genetic toolbox will be decisive in transforming B. methanolicus from a promising candidate into a fully established industrial workhorse for sustainable methanol-based biomanufacturing.

Luciana Fernandes Brito*
Markus Klitgaard Friis
Haowen Zhu
Trygve Brautaset
Volker F. Wendisch
Marta Irla*
Synth. Biol. Eng.
2025,
3
(4), 10016; 
DOI: 10.70322/sbe.2025.10016
Open Access

Review

17 November 2025

Enzyme-Mediated Carbon Dioxide Fixation: Catalytic Mechanisms and Computational Insights

Carbon conversion technologies that transform carbon dioxide (CO2) into high-value chemicals are pivotal for achieving sustainability. Among these, enzyme-mediated CO2 fixation has recently gained increasing attention as a more sustainable and environmentally friendly alternative to traditional chemical methods, which typically require harsh conditions and impose significant environmental costs. Recent advances in computer-aided techniques have greatly facilitated the mechanistic understanding of CO2-fixing enzymes and accelerated the development of enzyme-catalyzed carboxylation strategies. This review highlights recent progress in enzyme-mediated CO2 fixation by categorizing key enzymes into four classes based on their cofactor or metal ion requirements: cofactor-independent enzymes, metal-dependent enzymes, nicotinamide adenine dinucleotide phosphate (NAD(P)H)-dependent enzymes, and prenylated flavin mononucleotide (prFMN)-dependent enzymes. We outline the basic principles and applications of molecular dynamics (MD) simulations and quantum mechanical (QM) calculations, which serve as essential tools for investigating enzyme conformational dynamics and reaction mechanisms. Through representative case studies, we demonstrate how computational analyses uncover catalytic features that enhance CO2 conversion efficiency. These insights underscore the critical role of computer-aided approaches in guiding the rational design and optimization of biocatalysts, thereby advancing the application of enzyme-based systems for CO2 fixation.

Kai Wen
Jingxuan Zhu*
Quanshun Li*
Synth. Biol. Eng.
2025,
3
(4), 10017; 
DOI: 10.70322/sbe.2025.10017
Open Access

Review

26 November 2025

Prebiotic and Probiotic Foods in MASLD: Microbiome-Mediated Therapeutic Strategies

Through the use of prebiotics and probiotics, fermented foods offer significant health benefits by enhancing host nutrition and microbiota composition while providing distinctive flavor profiles. Fermentation substantially alters the bioactive compounds in these foods compared to their natural state. Additionally, fermented foods contain probiotics that can modulate consumers’ gut microbiomes, which in turn regulate host biochemistry to help combat various metabolic diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a growing global health burden. Gut microbiome dysbiosis, combined with unbalanced nutritional intake, is considered a primary driver of disease pathogenesis. Fermented foods can modify the bioavailability of micronutrients—including carbohydrates, polyphenols, and vitamins—thereby influencing host metabolism. Moreover, the probiotics present in fermented foods, along with their modulatory effects on the gut microbiota, contribute to both the management and prevention of MASLD. Modern fermentation approaches, leveraging synthetic biology, systems biology, and metabolic engineering, can further maximize these health benefits. This review summarizes the components, bioactive compounds, and mechanistic pathways by which fermented foods influence the pathogenesis of MASLD, and highlights the potential applications of modern fermentation technologies to enhance their health-promoting properties.

Beiming Cui
Yujie Liu
Joyce Hui-Eun Chang
Jieying Chen
Jiahang Xu
Jian-Peng Teoh
Chun Loong Ho*
Synth. Biol. Eng.
2025,
3
(4), 10018; 
DOI: 10.70322/sbe.2025.10018
Open Access

Review

08 December 2025

Advances in the Biosynthesis and Application of Sialyllactose

Human milk oligosaccharides (HMOs), the third most abundant solid component in human milk after lactose and lipids, are recognized as crucial prebiotics that support infant gut health and immune development. Salivary HMOs account for approximately 13% of the total HMOs molar ratio, with 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL) accounting for approximately 2% and 6%, respectively. Sialyllactose (SL) exhibits a range of notable physiological functions, including prebiotic activity, antiviral properties, prevention of necrotizing enterocolitis, immunomodulatory effects, and enhancement of brain development and cognition. Both 3′-SL and 6′-SL have been approved as “Generally Recognized as Safe” (GRAS) by the U.S. FDA and are increasingly incorporated into infant formula. Currently, the biosynthesis of SL is mainly efficiently produced through engineered microorganisms. However, face bottlenecks: low yields, complex downstream processing, and prohibitive costs. Recent advances in synthetic biology and metabolic engineering offer promising avenues to overcome these barriers. This review introduces the synthesis methods, functions, and applications of SL, as well as conducting safety evaluation and regulatory status analysis. We hope this article will enhance understanding of the challenges encountered in the synthetic biology production and application of SL.

Hong Wang
Hongtao Zhang*
Zimeng Zhang
Xu Chen
Xia Lai
Synth. Biol. Eng.
2025,
3
(4), 10019; 
DOI: 10.70322/sbe.2025.10019
Open Access

Review

11 December 2025

CRISPR-Armed Phages: Design, Mechanisms, Applications, and Prospects in Precision Microbiome Engineering

The dysregulation of microbial communities poses severe threats to host health and ecological stability, yet traditional microbiome modulation strategies lack specificity and often exacerbate dysbiosis. The CRISPR-Cas system offers unprecedented potential for targeted microbiome regulation due to its sequence-specific nucleic acid recognition and cleavage capabilities, but its translation is hindered by inefficient and non-specific delivery. As natural bacterial predators with inherent host specificity, bacteriophages have emerged as ideal carriers to address this delivery bottleneck. The development of CRISPR-armed phages combines the targeted delivery of phages and the precision editing advantages of CRISPR-Cas systems. This review systematically elaborates on the design and mechanism of CRISPR-armed phages for microbiome engineering. CRISPR-Cas systems were classified on the basis of their structural and functional characteristics, as well as their regulatory effects, in detail after phage delivery. The engineering strategies of integrative and non-integrative phage vectors were then discussed, followed by their applications in ecological regulation and genetic regulation of the microbiome. The current limitations were finally analyzed, such as narrow phage host range, bacterial phage resistance, and low editing efficiency. This review provides a comprehensive theoretical framework to promote the development of CRISPR-armed phages, aiming to advance precision microbiome engineering for human health.

Yuanming Ye
Juntao Shen
Zhilong Xiu*
Synth. Biol. Eng.
2025,
3
(4), 10020; 
DOI: 10.70322/sbe.2025.10020
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