Advances in research on the bio-production of 1,4-butanediol by the engineered microbes

1,4-butanediol (1,4-BDO) is an important building block in the chemical industry, which can be used to produce different products including tetrahydrofuran, γ-butyrolactone, polybutylene terephthalate, and polybutylene succinate. It has a broad application in pharmaceuticals, chemicals, materials, light industry and many other fields. The petroleum-based chemical synthesis method is the main route to produce 1,4-BDO but faces several issues such as non-renewability of raw materials, severe environmental pollution, complicated catalysis conditions and high production cost. The bio-based conversion method, relying on the microbial cell factories, is hence explored to produce 1,4-BDO owing to its advantages of environmental friendliness and green sustainability. In this work, the current status of the research on the production of 1,4-BDO by the engineered microbial cell factories was reviewed in terms of four aspects: (1) the multiple gene targets for overproducing 1,4-BDO; (2) the debottlenecking of rate-limiting steps in the synthesis pathway; (3) the control of the central carbon flux in 1,4-BDO synthesis; (4) the construction of novel pathways to convert different carbon sources to 1,4-BDO. The challenges and prospects were finally discussed and future works were proposed for the industrial production of 1,4-BDO by the bio-based method.