立足生物材料科学前沿，以高技术生物材料开发为重点，引导传统产业的技术更新和产品换代，是满足我国社会和经济发展需求的重要保障。新型生物材料－聚羟基脂肪酸酯(PHA)因其单体结构单一、合成途径复杂、合成机理不明等因素限制了其应用范围。本项目基于申请人利用体外合成体系通过聚合酶改造开发新型结构PHA的多年研究成果，拟开展基于PHA聚合酶定点突变的新型共聚酯P(3HB-co-HBZ)的生物合成研究：1)基于分子模拟构建PHA聚合酶phaC1的3D模型，设计具有聚合羟基苯甲酸能力的定点突变体。2)通过自主设计的体外合成体系验证共聚酯P(3HB-co-HBZ)合成。3)基于体外合成途径构建基因工程菌，实现主链含有苯环的非天然共聚酯P(3HB-co-HBZ)微生物自组装生产。本项目将在phaC1酶学改造、新型结构PHA合成途径设计及微生物自组装生产方面实现突破，为其它新型生物材料的开发提供理论基础。

It is an important guarantee to meet the needs of social and economic development of our country to guide the technological renewal and product replacement of traditional industries, basing on the development of high-tech biomaterials. Due to single monomer structure, complex synthesis pathway and unknown synthetic mechanism of Polyhydroxyalkanoate (PHA), the application of new biomaterial is limited. Based on the applicant's research achievements in the field of new structure PHA synthesis for many years, this project intends to carry out the research on Biosynthesis of a Novel Co-polymer P(3HB-co-HBZ)by Site-directed Mutagenesis of PHA Polymerase：(1) the 3D structure model of PHA polymerase phaC1 is constructed based on molecular simulation，and a site-directed mutant with the ability to polymerize hydroxybenzoic acid was designed. (2) the synthesis of co-polyester P (3HB-co-HBZ) was validated by self-designed in vitro synthesis system. (3) based on the synthetic pathway in vitro, constructed genetically engineered bacteria by molecular means to realize the microbial self-assembly fermentation of co-polyester P (3HB-co-HBZ) containing benzene rings in the main chain. This project achieves breakthroughs in phaC1 enzymatic modification, new structure PHA synthetic pathway design and microbial self-assembly production, and provides theoretical basis for the development of other new biomaterials.