PMID- 37526330 OWN - NLM STAT- Publisher LR - 20231013 IS - 1097-0290 (Electronic) IS - 0006-3592 (Linking) VI - 120 IP - 11 DP - 2023 Nov TI - Intracellular accumulation of c-di-GMP and its regulation on self-flocculation of the bacterial cells of Zymomonas mobilis. PG - 3234-3243 LID - 10.1002/bit.28513 [doi] AB - Zymomonas mobilis is an emerging chassis for being engineered to produce bulk products due to its unique glycolysis through the Entner-Doudoroff pathway with less ATP produced for lower biomass accumulation and higher product yield. When self-flocculated, the bacterial cells are more productive, since they can self-immobilize within bioreactors for high density, and are more tolerant to stresses for higher product titers, but this morphology needs to be controlled properly to avoid internal mass transfer limitation associated with their strong self-flocculation. Herewith we explored the regulation of cyclic diguanosine monophosphate (c-di-GMP) on self-flocculation of the bacterial cells through activating cellulose biosynthesis. While ZMO1365 and ZMO0919 with GGDEF domains for diguanylate cyclase activity catalyze c-di-GMP biosynthesis, ZMO1487 with an EAL domain for phosphodiesterase activity catalyzes c-di-GMP degradation, but ZMO1055 and ZMO0401 contain the dual domains with phosphodiesterase activity predominated. Since c-di-GMP is synthesized from GTP, the intracellular accumulation of this signal molecule through deactivating phosphodiesterase activity is preferred for activating cellulose biosynthesis to flocculate the bacterial cells, because such a strategy exerts less perturbance on intracellular processes regulated by GTP. These discoveries are significant for not only engineering unicellular Z. mobilis strains with the self-flocculating morphology to boost production but also understanding mechanism underlying c-di-GMP biosynthesis and degradation in the bacterium. CI - (c) 2023 Wiley Periodicals LLC. FAU - Li, Kai AU - Li K AD - State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Science, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. FAU - Xia, Juan AU - Xia J AD - State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Science, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. FAU - Liu, Chen-Guang AU - Liu CG AUID- ORCID: 0000-0003-0343-6304 AD - State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Science, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. FAU - Zhao, Xin-Qing AU - Zhao XQ AD - State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Science, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. FAU - Bai, Feng-Wu AU - Bai FW AUID- ORCID: 0000-0003-1431-4839 AD - State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Science, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. LA - eng GR - National Natural Science Foundation of China/ PT - Journal Article DEP - 20230801 PL - United States TA - Biotechnol Bioeng JT - Biotechnology and bioengineering JID - 7502021 SB - IM OTO - NOTNLM OT - Zymomonas mobilis OT - c-di-GMP OT - chassis OT - industrial production OT - microbial cell factories OT - self-flocculation EDAT- 2023/08/01 13:11 MHDA- 2023/08/01 13:11 CRDT- 2023/08/01 08:13 PHST- 2023/06/26 00:00 [revised] PHST- 2023/03/27 00:00 [received] PHST- 2023/07/17 00:00 [accepted] PHST- 2023/08/01 13:11 [pubmed] PHST- 2023/08/01 13:11 [medline] PHST- 2023/08/01 08:13 [entrez] AID - 10.1002/bit.28513 [doi] PST - ppublish SO - Biotechnol Bioeng. 2023 Nov;120(11):3234-3243. doi: 10.1002/bit.28513. Epub 2023 Aug 1.