Intracellular accumulation of c-di-GMP and its regulation on self-flocculation of the bacterial cells of Zymomonas mobilis
Intracellular accumulation of c-di-GMP and its regulation on self-flocculation of the bacterial cells of Zymomonas mobilis
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DOI：
10.1002/bit.28513
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发表时间：
2023-08-01
影响因子：
3.8
通讯作者：
Bai，Feng-Wu
中科院分区：
文献类型：
--
作者：
Li，Kai;Xia，Juan;Bai，Feng-Wu
运动发酵单胞菌是一种新兴的底盘，可用于生产散装产品，因为它通过 Entner-Doudoroff 途径进行独特的糖酵解，产生的 ATP 较少，从而降低了生物量积累并提高了产品产量。当自絮凝时，细菌细胞的生产力更高，因为它们可以在生物反应器内自我固定以获得高密度，并且更能耐受压力以获得更高的产品滴度，但这种形态需要适当控制，以避免与其强自絮凝相关的内部传质限制。在此，我们探索了环二鸟苷单磷酸（c-di-GMP）通过激活纤维素生物合成对细菌细胞自絮凝的调节。具有二鸟苷酸环化酶活性的 GGDEF 结构域的 ZMO1365 和 ZMO0919 催化 c-di-GMP 生物合成，具有磷酸二酯酶活性的 EAL 结构域的 ZMO1487 催化 c-di-GMP 降解，但 ZMO1055 和 ZMO0401 包含以磷酸二酯酶活性为主的双结构域。由于 c-di-GMP 是由 GTP 合成的，因此通过灭活磷酸二酯酶活性来在细胞内积累该信号分子是激活纤维素生物合成以絮凝细菌细胞的首选，因为这种策略对 GTP 调节的细胞内过程产生的干扰较小。这些发现不仅对于单细胞 Z 工程具有重要意义。具有自絮凝形态的流动菌株可提高产量，同时也了解细菌中 c-di-GMP 生物合成和降解的潜在机制。
Zymomonas mobilisis 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 unicellularZ. mobilisstrains with the self‐flocculating morphology to boost production but also understanding mechanism underlying c‐di‐GMP biosynthesis and degradation in the bacterium.