PMID- 34728789 OWN - NLM STAT- MEDLINE DCOM- 20211220 LR - 20230208 IS - 2399-3642 (Electronic) IS - 2399-3642 (Linking) VI - 4 IP - 1 DP - 2021 Nov 2 TI - An oxidative metabolic pathway of 4-deoxy-L-erythro-5-hexoseulose uronic acid (DEHU) from alginate in an alginate-assimilating bacterium. PG - 1254 LID - 10.1038/s42003-021-02786-8 [doi] LID - 1254 AB - Alginate-assimilating bacteria degrade alginate into an unsaturated monosaccharide, which is converted into 4-deoxy-L-erythro-5-hexoseulose uronic acid (DEHU). DEHU is reduced to 2-keto-3-deoxy-D-gluconate by a DEHU-specific reductase using NAD(P)H. This is followed by pyruvate production via the Entner-Doudoroff pathway. Previously, we identified FlRed as a DEHU reductase in an alginate-assimilating bacterium, Flavobacterium sp. strain UMI-01. Here, we showed that FlRed can also catalyze the oxidation of DEHU with NAD(+), producing 2-keto-3-deoxy-D-glucarate (KDGR). FlRed showed a predilection for NADH and NAD(+) over NADPH and NADP(+), respectively, and the K(m) value for NADH was approximately 2.6-fold less than that for NAD(+). Furthermore, we identified two key enzymes, FlDet and FlDeg, for KDGR catabolism. FlDet was identified as an enzyme of the ribonuclease activity regulator A family, which converts KDGR to alpha-ketoglutaric semialdehyde (alpha-KGSA). FlDeg, a type II alpha-KGSA dehydrogenase, generated alpha-ketoglutaric acid by oxidizing the aldehyde group of alpha-KGSA using NAD(P)(+). Consequently, unlike the conventional DEHU reduction pathway, DEHU can be directly converted to alpha-ketoglutaric acid without consuming NAD(P)H. Alginate upregulated the expression of not only FlRed and two enzymes of the DEHU-reduction pathway, but also FlDet and FlDeg. These results revealed dual pathways of DEHU metabolism involving reduction or oxidation by FlRed. CI - (c) 2021. The Author(s). FAU - Nishiyama, Ryuji AU - Nishiyama R AD - Graduate School of Fisheries Sciences, Hokkaido University, Hakodate, Hokkaido, Japan. FAU - Ojima, Takao AU - Ojima T AD - Graduate School of Fisheries Sciences, Hokkaido University, Hakodate, Hokkaido, Japan. FAU - Ohnishi, Yuki AU - Ohnishi Y AD - Faculty of Advanced Life Science, Hokkaido University, Sapporo, Hokkaido, Japan. FAU - Kumaki, Yasuhiro AU - Kumaki Y AD - Faculty of Science, Hokkaido University, Sapporo, Hokkaido, Japan. FAU - Aizawa, Tomoyasu AU - Aizawa T AD - Faculty of Advanced Life Science, Hokkaido University, Sapporo, Hokkaido, Japan. FAU - Inoue, Akira AU - Inoue A AUID- ORCID: 0000-0002-6049-3412 AD - Graduate School of Fisheries Sciences, Hokkaido University, Hakodate, Hokkaido, Japan. inouea21@fish.hokudai.ac.jp. LA - eng GR - 16H04977/MEXT | Japan Society for the Promotion of Science (JSPS)/ GR - 19H0303909/MEXT | Japan Society for the Promotion of Science (JSPS)/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211102 PL - England TA - Commun Biol JT - Communications biology JID - 101719179 RN - 0 (Alginates) RN - 0 (Uronic Acids) SB - IM MH - Alginates/*metabolism MH - Flavobacterium/*metabolism MH - *Metabolic Networks and Pathways MH - Oxidation-Reduction MH - Uronic Acids/*metabolism PMC - PMC8563752 COIS- The authors declare no competing interests. EDAT- 2021/11/04 06:00 MHDA- 2021/12/21 06:00 PMCR- 2021/11/02 CRDT- 2021/11/03 06:50 PHST- 2020/03/16 00:00 [received] PHST- 2021/10/14 00:00 [accepted] PHST- 2021/11/03 06:50 [entrez] PHST- 2021/11/04 06:00 [pubmed] PHST- 2021/12/21 06:00 [medline] PHST- 2021/11/02 00:00 [pmc-release] AID - 10.1038/s42003-021-02786-8 [pii] AID - 2786 [pii] AID - 10.1038/s42003-021-02786-8 [doi] PST - epublish SO - Commun Biol. 2021 Nov 2;4(1):1254. doi: 10.1038/s42003-021-02786-8.