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Biosynthesis pathways and strategies for improving 3-hydroxypropionic acid production in bacteria

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Abstract

3-Hydroxypropionic acid (3-HP) represents an economically important platform compound from which a panel of bulk chemicals can be derived. Compared with petroleum-dependent chemical synthesis, bioproduction of 3-HP has attracted more attention due to utilization of renewable biomass. This review outlines bacterial production of 3-HP, covering aspects of host strains (e.g., Escherichia coli and Klebsiella pneumoniae), metabolic pathways, key enzymes, and hurdles hindering high-level production. Inspired by the state-of-the-art advances in metabolic engineering and synthetic biology, we come up with protocols to overcome the hurdles constraining 3-HP production. The protocols range from rewiring of metabolic networks, alleviation of metabolite toxicity, to dynamic control of cell size and density. Especially, this review highlights the substantial contribution of microbial growth to 3-HP production, as we recognize the synchronization between cell growth and 3-HP formation. Accordingly, we summarize the following growth-promoting strategies: (i) optimization of fermentation conditions; (ii) construction of gene circuits to alleviate feedback inhibition; (iii) recruitment of RNA polymerases to overexpress key enzymes which in turn boost cell growth and 3-HP production. Lastly, we propose metabolic engineering approaches to simplify downstream separation and purification. Overall, this review aims to portray a picture of bacterial production of 3-HP.

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Acknowledgements

This study was funded by grants from Hebei Project for the Development of Science and Technology Guided by Central Universities (206Z2902G) and National Key Research and Development Program of China (2018YFA0901800), National Natural Science Foundation of China (21476011) and National High Technology Research and Development Program (863 Program, 2015AA021003).

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  1. Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, People’s Republic of China

    Peng Zhao & Pingfang Tian

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  1. Peng Zhao
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Zhao, P., Tian, P. Biosynthesis pathways and strategies for improving 3-hydroxypropionic acid production in bacteria. World J Microbiol Biotechnol 37, 117 (2021). https://doi.org/10.1007/s11274-021-03091-6

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