Engineering Bacillus subtilis for the conversion of the antimetabolite 4-hydroxy-l-threonine to pyridoxine

Metabolic Engineering
Fabian M CommichauZoltán Prágai

Abstract

Until now, pyridoxine (PN), the most commonly supplemented B6 vitamer for animals and humans, is chemically synthesized for commercial purposes. Thus, the development of a microbial fermentation process is of great interest for the biotech industry. Recently, we constructed a Bacillus subtilis strain that formed significant amounts of PN via a non-native deoxyxylulose 5'-phosphate-(DXP)-dependent vitamin B6 pathway. Here we report the optimization of the condensing reaction of this pathway that consists of the 4-hydroxy-l-threonine-phosphate dehydrogenase PdxA, the pyridoxine 5'-phosphate synthase PdxJ and the native DXP synthase, Dxs. To allow feeding of high amounts of 4-hydroxy-threonine (4-HO-Thr) that can be converted to PN by B. subtilis overexpressing PdxA and PdxJ, we first adapted the bacteria to tolerate the antimetabolite 4-HO-Thr. The adapted bacteria produced 28-34mg/l PN from 4-HO-Thr while the wild-type parent produced only 12mg/l PN. Moreover, by expressing different pdxA and pdxJ alleles in the adapted strain we identified a better combination of PdxA and PdxJ enzymes than reported previously, and the resulting strain produced 65mg/l PN. To further enhance productivity mutants were isolated that efficiently tak...Continue Reading

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Citations

Jun 14, 2016·ACS Chemical Biology·Jennifer J ThiavilleValérie de Crécy-Lagard
May 23, 2017·Nature Reviews. Microbiology·Laurence ZitvogelGuido Kroemer
Jul 8, 2017·Journal of Agricultural and Food Chemistry·Tomokazu ItoTohru Yoshimura
Jan 23, 2019·Environmental Microbiology·Dennis WickeFabian M Commichau
Jun 5, 2016·Molecular Microbiology·Jonathan RosenbergFabian M Commichau
Aug 5, 2017·Microbial Biotechnology·Daniel R ReußJörg Stülke
Oct 14, 2017·Environmental Microbiology·Jonathan RosenbergFabian M Commichau
Aug 9, 2020·Microbiology Resource Announcements·Björn RichtsFabian M Commichau
May 28, 2019·Frontiers in Molecular Biosciences·Björn RichtsFabian M Commichau
Mar 6, 2021·Applied Microbiology and Biotechnology·Björn Richts, Fabian M Commichau
May 25, 2021·Seminars in Cancer Biology·Haoyue GuoYang Yang
Apr 21, 2021·Environmental Microbiology·Robert HertelFabian M Commichau
Jul 6, 2021·Frontiers in Bioengineering and Biotechnology·Yanyan WangDawei Zhang

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