Lu Chunzhe, Weusthuis Ruud A
Bioprocess Engineering, Wageningen University & Research, Wageningen, The Netherlands; Groningen Biomolecular Sciences & Biotechnology Institute, University of Groningen 9747 AG Groningen, The Netherlands.
Bioprocess Engineering, Wageningen University & Research, Wageningen, The Netherlands.
Bioresour Technol. 2025 Nov;435:132932. doi: 10.1016/j.biortech.2025.132932. Epub 2025 Jul 1.
Medium-chain-length α,ω-diols (mcl-diols) are valuable and versatile molecules with applications in polymers, lubricants, and specialty chemicals. Currently, their production relies on fossil-based industrial processes, but there is a growing effort to develop sustainable alternatives. Microbial biosynthesis has emerged as a promising approach, with successful mcl-diols production from various renewable substrates, including n-alkanes, fatty acids, cycloalkanes, adipic acid, and glucose. This review summarizes and compares different microbial mcl-diols biosynthetic pathways, highlighting their strengths and limitations. A generalized pathway applicable to various chain lengths is proposed, based on fatty acid biosynthesis or the reversed β-oxidation pathway. Critical challenges remain, such as accelerating microbial chassis selection and optimization, enhancing the activity of rate-limiting enzymes, and mitigating the toxicity of intermediates and end products. To accelerate the commercialization of microbial mcl-diols production, future efforts should focus on metabolic engineering strategies, advanced protein engineering techniques, and process optimization. Additionally, the integration of synthetic biology, adaptive laboratory evolution, and AI-driven enzyme design can further enhance pathway efficiency and reduce production costs. This review provides insights into the current progress and future directions for sustainable mcl-diols biosynthesis, contributing to the broader goal of replacing fossil-based chemicals with bio-based alternatives.
中链长度的α,ω-二醇（mcl-二醇）是有价值且用途广泛的分子，在聚合物、润滑剂和特种化学品中都有应用。目前，它们的生产依赖于基于化石的工业过程，但开发可持续替代方法的努力正在不断增加。微生物生物合成已成为一种有前景的方法，已成功地从各种可再生底物生产出mcl-二醇，这些底物包括正构烷烃、脂肪酸、环烷烃、己二酸和葡萄糖。本综述总结并比较了不同的微生物mcl-二醇生物合成途径，突出了它们的优势和局限性。基于脂肪酸生物合成或反向β-氧化途径，提出了一种适用于各种链长的通用途径。仍然存在一些关键挑战，例如加快微生物底盘的选择和优化、提高限速酶的活性以及减轻中间体和终产物的毒性。为了加速微生物生产mcl-二醇的商业化，未来的努力应集中在代谢工程策略、先进的蛋白质工程技术和工艺优化上。此外，合成生物学、适应性实验室进化和人工智能驱动的酶设计的整合可以进一步提高途径效率并降低生产成本。本综述深入探讨了可持续mcl-二醇生物合成的当前进展和未来方向，有助于实现用生物基替代品取代基于化石的化学品这一更广泛的目标。
