Key Laboratory of Molecular Microbiology and Technology for Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
Department of Biochemistry and Molecular Biology, College of Life Sciences, Nankai University, Tianjin, China.
Biotechnol Bioeng. 2024 Jul;121(7):2106-2120. doi: 10.1002/bit.28694. Epub 2024 Apr 8.
Microbial production of polyhydroxyalkanoate (PHA) is greatly restricted by high production cost arising from high-temperature sterilization and expensive carbon sources. In this study, a low-cost PHA production platform was established from Halomonas cupida J9. First, a marker-less genome-editing system was developed in H. cupida J9. Subsequently, H. cupida J9 was engineered to efficiently utilize xylose for PHA biosynthesis by introducing a new xylose metabolism module and blocking xylonate production. The engineered strain J9UΔxylD-P8xylA has the highest PHA yield (2.81 g/L) obtained by Halomonas with xylose as the sole carbon source so far. This is the first report on the production of short- and medium-chain-length (SCL-co-MCL) PHA from xylose by Halomonas. Interestingly, J9UΔxylD-P8xylA was capable of efficiently utilizing glucose and xylose as co-carbon sources for PHA production. Furthermore, fed-batch fermentation of J9UΔxylD-P8xylA coupled to a glucose/xylose co-feeding strategy reached up to 12.57 g/L PHA in a 5-L bioreactor under open and unsterile condition. Utilization of corn straw hydrolysate as the carbon source by J9UΔxylD-P8xylA reached 7.0 g/L cell dry weight (CDW) and 2.45 g/L PHA in an open fermentation. In summary, unsterile production in combination with inexpensive feedstock highlights the potential of the engineered strain for the low-cost production of PHA from lignocellulose-rich agriculture waste.
微生物聚羟基脂肪酸酯(PHA)的生产受到高温灭菌和昂贵碳源导致高生产成本的极大限制。在本研究中,从盐单胞菌(Halomonas cupida)J9 建立了一个低成本的 PHA 生产平台。首先,在 H. cupida J9 中开发了无标记基因组编辑系统。随后,通过引入新的木糖代谢模块和阻断木酸盐生成,工程菌株 J9UΔxylD-P8xylA 有效地利用木糖进行 PHA 生物合成。该工程菌株 J9UΔxylD-P8xylA 是迄今为止利用木糖作为唯一碳源获得最高 PHA 产量(2.81 g/L)的盐单胞菌。这是第一份关于盐单胞菌利用木糖生产短链和中链长度(SCL-co-MCL)PHA 的报告。有趣的是,J9UΔxylD-P8xylA 能够有效地利用葡萄糖和木糖作为共碳源进行 PHA 生产。此外,在开放和非无菌条件下,通过葡萄糖/木糖共补料策略,J9UΔxylD-P8xylA 的补料分批发酵在 5-L 生物反应器中达到了 12.57 g/L PHA。J9UΔxylD-P8xylA 利用玉米秸秆水解物作为碳源,在开放发酵中达到了 7.0 g/L 细胞干重(CDW)和 2.45 g/L PHA。总之,非无菌生产与廉价原料相结合突出了工程菌株在利用富含木质纤维素的农业废弃物低成本生产 PHA 方面的潜力。