Paduvari Raghavendra, Somashekara Divyashree Mysore
Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, India.
Bioengineered. 2025 Dec;16(1):2458363. doi: 10.1080/21655979.2025.2458363. Epub 2025 Jan 30.
Polyhydroxyalkanoates (PHA) are bioplastics produced by few bacteria as intracellular lipid inclusions under excess carbon source and nutrient-deprived conditions. These polymers are biodegradable and resemble petroleum-based plastics. The rising environmental concerns have increased the demand for PHA, but the low yield in wild-type bacterial strains limits large-scale production. An improvement in the PHA production can be achieved by genetically engineering the wild-type bacterial strains by removing competitive pathways that divert the metabolites away from PHA biosynthesis, cloning strong promotors to overexpress the genes involved in PHA biosynthesis and constructing non-native metabolic pathways that feed the metabolites for PHA production. The desired monomers in the PHA polymers were obtained by elimination of genes involved in PHA biosynthetic pathway. The chain length degradation specific-gene deletion of β-oxidation pathway resulted in the accumulation of PHA monomers having high carbon chain length. A controlled accumulation of monomers in the PHA polymer was achieved by constructing novel pathways in the bacteria and deleting native genes of competitive pathways from the genome of non-PHA producers. The present review attempts to showcase the novel genetic modification approaches conducted so far to enhance the PHA production with a special focus on metabolic pathway gene deletion in various bacteria.
聚羟基脂肪酸酯(PHA)是少数细菌在碳源过剩和营养缺乏条件下作为细胞内脂质内含物产生的生物塑料。这些聚合物是可生物降解的,并且类似于石油基塑料。日益增长的环境问题增加了对PHA的需求,但野生型细菌菌株的低产量限制了大规模生产。通过对野生型细菌菌株进行基因工程改造,可以提高PHA的产量,具体方法包括去除使代谢物从PHA生物合成中转移的竞争途径、克隆强启动子以过表达参与PHA生物合成的基因,以及构建为PHA生产提供代谢物的非天然代谢途径。通过消除参与PHA生物合成途径的基因,可获得PHA聚合物中所需的单体。β-氧化途径的链长降解特异性基因缺失导致了具有高碳链长度的PHA单体的积累。通过在细菌中构建新途径并从非PHA生产者的基因组中删除竞争途径的天然基因,实现了PHA聚合物中单体的可控积累。本综述试图展示迄今为止为提高PHA产量而进行的新型基因改造方法,特别关注各种细菌中的代谢途径基因缺失。