Engineering Halomonas bluephagenesis for Pilot Production of Terpolymers Containing 3-Hydroxybutyrate, 4-Hydroxybutyrate and 3-Hydroxyvalerate) from Glucose.

IF 6.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Metabolic engineering Pub Date : 2025-03-11 DOI:10.1016/j.ymben.2025.03.003
Hongtao He, Ng Wuh Jer, Qitiao Hu, Zhongnan Zhang, Simian Sun, Geyuan Xu, Shimao Yang, Shuang Zheng, Fuqing Wu, Qiong Wu, Guo-Qiang Chen
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引用次数: 0

Abstract

Microbial poly(3-hydroxybutyrate-co-4-hydroxybutyrate-co-3-hydroxyvalerate), abbreviated as P(3HB-4HB-3HV) or P34HBHV, is a flexible polyhydroxyalkanoate (PHA) material ranging from softness to elasticity depending on the ratios of various monomers. Halomonas bluephagenesis, as the chassis of the next generation industrial biotechnology (NGIB) able to grow contamination free under open unsterile conditions. The resulting recombinants of H. bluephagenesis became capable of efficiently synthesizing P34HBHV utilizing glucose as the sole carbon source. Engineered H. bluephagenesis H1 (encoding ogdA, sucD, 4hbD, orfZ, scpA and scpB in chromosomes) transformed with a plasmid containing PHA synthesis genes phaC and phaA and its derivative H29 produced up to 92% P(3HB-co-8.85%4HB-co-8.47%3HV) and 72% P(3HB-co-13.21%4HB-co-11.97%3HV) in cell dry weight (CDW), respectively, in shake flasks. In bioreactor cultivation, H. bluephagenesis H39 constructed by integrating the 4hbD, phaC and phaA genes into the genome of H. bluephagenesis H1 achieved 95 g/L CDW with 69% P(3HB-co-10.49%4HB-co-3.54%3HV), while H. bluephagenesis H43, further optimized with lpxM deletion, reached 73 g/L CDW with 78% P(3HB-co-10.35%4HB-co-4.54%3HV) in a 100 L bioreactor. For the first time, H. bluephagenesis was successfully engineered to generate stable and hyperproductive derivative strains for pilot production of P(3HB-4HB-3HV) with customizable monomer ratios from glucose as the sole carbon source.

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来源期刊
Metabolic engineering
Metabolic engineering 工程技术-生物工程与应用微生物
CiteScore
15.60
自引率
6.00%
发文量
140
审稿时长
44 days
期刊介绍: Metabolic Engineering (MBE) is a journal that focuses on publishing original research papers on the directed modulation of metabolic pathways for metabolite overproduction or the enhancement of cellular properties. It welcomes papers that describe the engineering of native pathways and the synthesis of heterologous pathways to convert microorganisms into microbial cell factories. The journal covers experimental, computational, and modeling approaches for understanding metabolic pathways and manipulating them through genetic, media, or environmental means. Effective exploration of metabolic pathways necessitates the use of molecular biology and biochemistry methods, as well as engineering techniques for modeling and data analysis. MBE serves as a platform for interdisciplinary research in fields such as biochemistry, molecular biology, applied microbiology, cellular physiology, cellular nutrition in health and disease, and biochemical engineering. The journal publishes various types of papers, including original research papers and review papers. It is indexed and abstracted in databases such as Scopus, Embase, EMBiology, Current Contents - Life Sciences and Clinical Medicine, Science Citation Index, PubMed/Medline, CAS and Biotechnology Citation Index.
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