bims-livmat 2025-04-06 papers

J Biotechnol. 2025 Mar 26. pii: S0168-1656(25)00073-2. [Epub ahead of print]403 52-72

Microbial production of hyaluronic acid: The current advances, engineering strategies and trends.

Ehab Marwan-Abdelbaset, Mohamed Samy-Kamal, Dan Tan, XiaoYun Lu.

Hyaluronic acid (HA) is a versatile biomolecule with applications in medicine, cosmetics, and pharmaceuticals. While traditionally extracted from animal tissues, HA is now predominantly produced through microbial fermentation. Microbial fermentation using strains such as Streptococcus zooepidemicus, Corynebacterium glutamicum, and Bacillus subtilis offers a more scalable and sustainable alternative to chemical and animal extraction methods. Recent studies reveal promising yields from engineered strains of Corynebacterium glutamicum and Bacillus subtilis, utilizing advanced metabolic and genetic techniques. Recent advancements in genetic and metabolic engineering, as well as synthetic biology, have addressed some challenges related to molecular weight, viscosity, and by-product formation. This review focuses on the microbial production of HA using engineered strains, encompassing producer organisms, metabolic engineering strategies, industrial-scale production, and key factors influencing molecular weight. Furthermore, it addresses the challenges and potential solutions associated with HA production. Additional research is necessary to develop more efficient and robust engineered strains that exhibit resistance to contamination and can utilize low-cost substrates, such as Pseudomonas putida and Halomonas spp. By overcoming these challenges, researchers can advance the industrial production of HA and expand its applications, thereby contributing to the growth of the HA market.

Keywords: Hyaluronan synthase; Hyaluronic acid; Metabolic engineering; Microbial Production; Molecular weight

DOI: https://doi.org/10.1016/j.jbiotec.2025.03.015

ACS Synth Biol. 2025 Apr 02.

Development of a Transposon-Based Genome Engineering Toolkit for Efficient and Adaptable Genetic Modifications in Wolfiporia cocos.

Seungwoo Baek, Bogun Kim, Duleepa Pathiraja, In-Geol Choi.

Advances in genome engineering of fungal strains are rapidly progressing, driven by the increasing interest in fungal biotechnology. Given the unique genomic and cellular complexity of fungi, each strain benefits from a tailored toolkit for efficient genome engineering. Here, we present a transposon-based engineering toolkit specifically optimized for Wolfiporia cocos, a species valued for its bioactive compounds. This toolkit significantly improves transformation efficiency, enabling multiplexed gene integration and facilitating rapid, flexible prototyping by assembling multiple genes into transposomes in a cocktail format, which bypasses the need for an intricate genetic circuit assembly. Engineered strains demonstrated stable expression across generations, as confirmed by successful genomic integration. Additionally, we identified six native W. cocos promoters from transcriptomic data, with two showing robust, constitutive expression in the mycelium of engineered strains. This transposon-based toolkit offers a versatile resource for synthetic biology, supporting efficient and adaptable genetic modifications within fungal systems.

Keywords: Tn5 transposon; Wolfiporia cocos; basidiomycete; biopart; genome engineering; native promoter; transformation

DOI: https://doi.org/10.1021/acssynbio.4c00766

Microb Cell Fact. 2025 Mar 29. 24(1): 75

Advances in synthesizing plant-derived isoflavones and their precursors with multiple pharmacological activities using engineered yeasts.

Wenhui Niu, Jingxian Zhang, Lingbo Qu, Xiao-Jun Ji, Yongjun Wei.

Isoflavones such as daidzein and genistein are naturally occurring compounds found in plants such as legumes. They have diverse pharmacological activities, making them valuable in the food, pharmaceutical, and cosmetic industries. Currently, isoflavones are mainly obtained through the extraction of plant biomass. Chemical synthesis is challenging for most isoflavones due to the complexity of their structures. The limited supply of isoflavones cannot meet the market demands. Advances in synthetic biology have provided a sustainable and efficient solution for the production of isoflavones, with yeasts often serving as the microbial chassis for biosynthesis. This review summarizes the pharmacological properties of specific isoflavones, their biosynthetic pathways, and the technical strategies used in engineered yeasts for isoflavone production. In addition, the development of synthetic biology and state-of-the-art biotechnological strategies for the environmentally friendly production of bioactive isoflavones is discussed.

Keywords: Engineered yeasts; Isoflavones; Metabolic pathways; Synthetic biology

DOI: https://doi.org/10.1186/s12934-025-02692-2

Microbiol Res. 2025 Mar 28. pii: S0944-5013(25)00112-0. [Epub ahead of print]296 128156

Unraveling the potential of bioengineered microbiome-based strategies to enhance cancer immunotherapy.

Muhammad Hamza, Shuai Wang, Yike Liu, Kun Li, Motao Zhu, Lin Chen.

The human microbiome plays a pivotal role in the field of cancer immunotherapy. The microbial communities that inhabit the gastrointestinal tract, as well as the bacterial populations within tumors, have been identified as key modulators of therapeutic outcomes, affecting immune responses and reprogramming the tumor microenvironment. Advances in synthetic biology have made it possible to reprogram and engineer these microorganisms to improve antitumor activity, enhance T-cell function, and enable targeted delivery of therapies to neoplasms. This review discusses the role of the microbiome in modulating both innate and adaptive immune mechanisms-ranging from the initiation of cytokine production and antigen presentation to the regulation of immune checkpoints-and discusses how these mechanisms improve the efficacy of immune checkpoint inhibitors. We highlight significant advances with bioengineered strains like Escherichia coli Nissle 1917, Lactococcus lactis, Bifidobacterium, and Bacteroides, which have shown promising antitumor efficacy in preclinical models. These engineered microorganisms not only efficiently colonize tumor tissues but also help overcome resistance to standard therapies by reprogramming the local immune environment. Nevertheless, several challenges remain, such as the requirement for genetic stability, effective tumor colonization, and the control of potential safety issues. In the future, the ongoing development of genetic engineering tools and the optimization of bacterial delivery systems are crucial for the translation of microbiome-based therapies into the clinic. This review highlights the potential of bioengineered microbiota as an innovative, personalized approach in cancer immunotherapy, bringing hope for more effective and personalized treatment options for patients with advanced malignancies.

Keywords: Bioengineering bacteria; Cancer; Escherichia coli Nissle 1917; Immune checkpoint inhibitors; Immunotherapy; Microbiome; Tumor microenvironment

DOI: https://doi.org/10.1016/j.micres.2025.128156