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提高用于培养肉生产的重组生长因子和血清蛋白产量。

Enhancing recombinant growth factor and serum protein production for cultivated meat manufacturing.

作者信息

Mainali Prashant, Chua Melvin Shen-Wei, Tan Ding-Jie, Loo Bernard Liat-Wen, Ow Dave Siak-Wei

机构信息

Agency for Science, Technology and Research (A*STAR), Bioprocessing Technology Institute (BTI), 20 Biopolis Way, Centros #06-01, Singapore, 138668, Republic of Singapore.

Food, Chemical and Biotechnology, Singapore Institute of Technology, 10 Dover Dr, Singapore, 138683, Republic of Singapore.

出版信息

Microb Cell Fact. 2025 Feb 16;24(1):41. doi: 10.1186/s12934-025-02670-8.

Abstract

The commercial growth factors (GFs) and serum proteins (SPs) contribute to the high cost associated with the serum-free media for cultivated meat production. Producing recombinant GFs and SPs in scale from microbial cell factories can reduce the cost of culture media. Escherichia coli is a frequently employed host in the expression recombinant GFs and SPs. This review explores critical strategies for cost reduction in GFs and SPs production, focusing on yield enhancement, product improvement, purification innovation, and process innovation. Firstly, the review discusses the use of fusion tags to increase the solubility and yield of GFs & SPs, highlighting various studies that have successfully employed these tags for yield enhancement. We then explore how tagging strategies can streamline and economize the purification process, further reducing production costs. Additionally, we address the challenge of low half-life in GFs and SPs and propose potential strategies that can enhance their stability. Furthermore, improvements in the E. coli chassis and cell engineering strategies are also described, with an emphasis on the key areas that can improve yield and identify areas for cost minimization. Finally, we discuss key bioprocessing areas which can facilitate easier scale-up, enhance yield, titer, and productivity, and ultimately lower long-term production costs. It is crucial to recognize that not all suggested approaches can be applied simultaneously, as their relevance varies with different GFs and SPs. However, integrating of multiple strategies is anticipated to yield a cumulative effect, significantly reducing production costs. This collective effort is expected to substantially decrease the price of cultivated meat, contributing to the broader goal of developing sustainable and affordable meat.

摘要

商业生长因子(GFs)和血清蛋白(SPs)使得用于培养肉生产的无血清培养基成本高昂。利用微生物细胞工厂大规模生产重组GFs和SPs能够降低培养基成本。大肠杆菌是表达重组GFs和SPs时常用的宿主。本综述探讨了降低GFs和SPs生产成本的关键策略,重点关注产量提高、产品改进、纯化创新和工艺创新。首先,综述讨论了使用融合标签来提高GFs和SPs的溶解度和产量,强调了各项成功利用这些标签提高产量的研究。接着,我们探讨标签策略如何简化和节约纯化过程,进一步降低生产成本。此外,我们应对GFs和SPs半衰期短的挑战,并提出可提高其稳定性的潜在策略。此外,还描述了大肠杆菌底盘和细胞工程策略的改进,重点关注可提高产量的关键领域以及确定成本最小化的领域。最后,我们讨论了关键生物加工领域,这些领域可促进更轻松的扩大规模、提高产量、滴度和生产率,并最终降低长期生产成本。必须认识到,并非所有建议的方法都能同时应用,因为它们的相关性因不同的GFs和SPs而异。然而,整合多种策略预计会产生累积效应,显著降低生产成本。这种共同努力有望大幅降低培养肉的价格,有助于实现开发可持续且价格合理的肉类这一更广泛的目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac12/11831813/a423d62dd588/12934_2025_2670_Fig1_HTML.jpg

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