Averesch Nils J H, Prima Alex, Krömer Jens O
Centre for Microbial Electrochemical Systems (CEMES), The University of Queensland, Brisbane, Australia.
Advanced Water Management Centre (AWMC), The University of Queensland, Brisbane, Australia.
Bioprocess Biosyst Eng. 2017 Aug;40(8):1283-1289. doi: 10.1007/s00449-017-1785-z. Epub 2017 May 20.
Saccharomyces cerevisiae is a popular organism for metabolic engineering; however, studies aiming at over-production of bio-replacement precursors for the chemical industry often fail to overcome proof-of-concept stage. When intending to show real industrial attractiveness, the challenge is twofold: formation of the target compound must be increased, while minimizing the formation of side and by-products to maximize titer, rate and yield. To tackle these, the metabolism of the organism, as well as the parameters of the process, need to be optimized. Addressing both we show that S. cerevisiae is well-suited for over-production of aromatic compounds, which are valuable in chemical industry and are particularly useful in space technology. Specifically, a strain engineered to accumulate chorismate was optimized for formation of para-hydroxybenzoic acid. Then a fed-batch bioreactor process was developed, which delivered a final titer of 2.9 g/L, a maximum rate of 18.625 mg/(g × h) and carbon-yields of up to 3.1 mg/g.
酿酒酵母是代谢工程中常用的生物；然而，旨在过量生产化学工业生物替代前体的研究往往未能超越概念验证阶段。当想要展现真正的工业吸引力时，挑战是双重的：必须增加目标化合物的形成，同时尽量减少副产物和杂质的形成，以实现最高的滴度、速率和产量。为了解决这些问题，需要优化生物体的代谢以及工艺参数。通过同时解决这两个问题，我们证明酿酒酵母非常适合过量生产芳香族化合物，这些化合物在化学工业中很有价值，在航天技术中尤其有用。具体而言，对经过工程改造以积累分支酸的菌株进行了优化，以形成对羟基苯甲酸。然后开发了一种补料分批生物反应器工艺，其最终滴度为2.9 g/L，最大速率为18.625 mg/(g×h)，碳产率高达3.1 mg/g。
