School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, Singapore.
Biotechnol Adv. 2013 Nov;31(6):903-14. doi: 10.1016/j.biotechadv.2013.02.001. Epub 2013 Feb 10.
Efficient production of biochemicals using engineered microbes as whole-cell biocatalysts requires robust cell viability. Robust viability leads to high productivity and improved bioprocesses by allowing repeated cell recycling. However, cell viability is negatively affected by a plethora of stresses, namely chemical toxicity and metabolic imbalances, primarily resulting from bio-synthesis pathways. Chemical toxicity is caused by substrates, intermediates, products, and/or by-products, and these compounds often interfere with important metabolic processes and damage cellular infrastructures such as cell membrane, leading to poor cell viability. Further, stresses on engineered cells are accentuated by metabolic imbalances, which are generated by heavy metabolic resource consumption due to enzyme overexpression, redistribution of metabolic fluxes, and impaired intracellular redox state by co-factor imbalance. To address these challenges, herein, we discuss a range of key microbial engineering strategies, substantiated by recent advances, to improve cell viability for commercially sustainable production of biochemicals from renewable resources.
利用工程化微生物作为全细胞生物催化剂高效生产生物化学物质需要强大的细胞活力。通过允许细胞重复回收，强大的活力可提高生产力并改善生物工艺。然而，细胞活力受到多种压力的负面影响，主要是由于生物合成途径导致的化学毒性和代谢失衡。化学毒性是由底物、中间体、产物和/或副产物引起的，这些化合物经常干扰重要的代谢过程并破坏细胞膜等细胞基础设施，导致细胞活力差。此外，由于酶过表达、代谢通量再分配以及辅因子失衡导致的细胞内氧化还原状态受损，代谢失衡加剧了对工程细胞的压力。为了解决这些挑战，本文讨论了一系列关键的微生物工程策略，这些策略最近取得了进展，旨在提高细胞活力，从而从可再生资源中进行具有商业可持续性的生物化学物质生产。
