Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis.
Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis.
复制标题
DOI：
10.1038/s41467-023-40947-x
复制
发表时间：
2023-09-12
影响因子：
16.6
通讯作者：
Marienhagen, Jan
中科院分区：
文献类型：
--
作者：
Tharmasothirajan, Apilaasha;Melcr, Josef;Linney, John;Gensch, Thomas;Krumbach, Karin;Ernst, Karla Marlen;Brasnett, Christopher;Poggi, Paola;Pitt, Andrew R.;Goddard, Alan D.;Chatgilialoglu, Alexandros;Marrink, Siewert J.;Marienhagen, Jan
营养保健品和药学上感兴趣的植物多酚的微生物合成代表了化学合成或植物提取的更环保的替代方案。然而，大多数多酚对微生物具有细胞毒性，因为它们被认为会对细胞完整性和运输过程产生负面影响。为了提高工程细胞工厂的生产性能，必须制定策略来减轻这些有害影响。在这里，我们利用谷氨酸棒杆菌检查了二苯乙烯类化合物白藜芦醇在细胞膜和细胞壁中的积累，并通过实验和分子动力学模拟揭示了该二苯乙烯类化合物的膜硬化作用。游离脂肪酸补充剂筛选确定棕榈酸和亚油酸是减弱白藜芦醇细胞毒性作用的合适添加剂，从而使产品效价提高三倍。这种抵消产物积累对膜损伤影响的经济有效的方法可以转移到其他多酚的微生物生产中，并且可能代表其他膜活性生物产品的工程目标。芳香族化合物对底盘菌株的固有毒性阻碍了生物生产的进一步改进。在这里，作者表明，在谷氨酸棒杆菌发酵中外源补充棕榈油酸或亚油酸可以减弱白藜芦醇的膜硬化作用。
Microbial synthesis of nutraceutically and pharmaceutically interesting plant polyphenols represents a more environmentally friendly alternative to chemical synthesis or plant extraction. However, most polyphenols are cytotoxic for microorganisms as they are believed to negatively affect cell integrity and transport processes. To increase the production performance of engineered cell factories, strategies have to be developed to mitigate these detrimental effects. Here, we examine the accumulation of the stilbenoid resveratrol in the cell membrane and cell wall during its production using Corynebacterium glutamicum and uncover the membrane rigidifying effect of this stilbenoid experimentally and with molecular dynamics simulations. A screen of free fatty acid supplements identifies palmitelaidic acid and linoleic acid as suitable additives to attenuate resveratrol’s cytotoxic effects resulting in a three-fold higher product titer. This cost-effective approach to counteract membrane-damaging effects of product accumulation is transferable to the microbial production of other polyphenols and may represent an engineering target for other membrane-active bioproducts. The inherent toxicity of the aromatic compounds to the chassis strain hampers further improvement of bioproduction. Here, the authors show that membrane rigidifying effect of resveratrol can be attenuated by exogenous supplementation of palmitelaidic acid or linoleic acid in fermentation of Corynebacterium glutamicum.
登录
查看更多内容
多酚：对健康和衰老中心血管系统的好处。
影响因子：
5.9
作者：
Khurana S;Venkataraman K;Hollingsworth A;Piche M;Tai TC
通讯作者：
Tai TC
影响因子：
4
作者：
Ingolfsson, Helgi I.;Thakur, Pratima;Herold, Karl F.;Hobart, E. Ashley;Ramsey, Nicole B.;Periole, Xavier;de Jong, Djurre H.;Zwama, Martijn;Yilmaz, Duygu;Hall, Katherine;Maretzky, Thorsten;Hemmings, Hugh C., Jr.;Blobel, Carl;Marrink, Siewert J.;Kocer, Armagan;Sack, Jon T.;Andersen, Olaf S.
通讯作者：
Andersen, Olaf S.
影响因子：
1.2
作者：
Arndt, Annette;Auchter, Marc;Eikmanns, Bernhard J.
通讯作者：
Eikmanns, Bernhard J.
影响因子：
3.8
作者：
Fabris, Sabrina;Momo, Federico;Stevanato, Roberto
通讯作者：
Stevanato, Roberto
影响因子：
5.3
作者：
Engels M;Kalia M;Rahmati S;Petersilie L;Kovermann P;van Putten MJAM;Rose CR;Meijer HGE;Gensch T;Fahlke C
通讯作者：
Fahlke C