Abstract
Oxygen is a vital parameter for pyrroloquinoline quinone (PQQ) biosynthesis. In this study, the effects of oxygen supply on the biosynthesis of PQQ were first investigated systematically with Hyphomicrobium denitrificans FJNU-6. Following a kinetic analysis of the specific cell growth rate (μx) and specific PQQ formation rate (μp) in 5 L benchtop fermentation systems at various oxygen supply levels ranging from 0 to 60%, a novel, two-stage oxygen supply strategy was developed for enhancing PQQ production and productivity. Moreover, the transcription of genes involved in methanol oxidation and PQQ biosynthesis was analyzed throughout the process to outline the effect of oxygen supply on cell metabolism. Furthermore, with constant feeding of methanol at 0–1 g/L after the initial methanol was consumed completely, the PQQ concentration and productivity reached 1070 mg/L and 7.64 mg/L/h, respectively, after 140 h in a 5-L fermenter. The two-stage oxygen supply strategy developed in this study provides an effective and economical strategy for the industrial production of PQQ.
Key Points
• A novel, two-stage oxygen supply strategy was developed for enhancing PQQ production and productivity.
•The transcription of genes involved in methanol oxidation and PQQ biosynthesis was regulated by changes in oxygen supply.
• This study offers an effective and economical strategy for industrial or large-scale production of PQQ.
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Funding
This study was funded by grants from the National Natural Science Foundation of China (Grant No. 21807011), Natural Science Foundation of Fujian Province (Grant No. 2018J01673), and the Special Scientific Research Fund of the Higher Education Institutions of Fujian Province (Grant No. JK2017012).
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KCR and HJZ conceived and designed the research. LMS, RY, and XHP conducted the experiments. YXW, LMS, and KCR analyzed the data. LMS and YXW wrote the manuscript. All authors read and approved the manuscript.
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Liu, M., Yang, X., Ren, Y. et al. Two-stage oxygen supply strategy for enhancing fed-batch production of pyrroloquinoline quinone in Hyphomicrobium denitrificans FJNU-6. Appl Microbiol Biotechnol 104, 6615–6622 (2020). https://doi.org/10.1007/s00253-020-10690-0
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DOI: https://doi.org/10.1007/s00253-020-10690-0