2012年8月14日 訊 /生物谷BIOON/ --近日，來(lái)自弗萊堡大學(xué)的研究者收集了細(xì)菌甲酸鹽轉(zhuǎn)移蛋白（細(xì)菌重要代謝過程的蛋白質(zhì)）精確數(shù)據(jù)信息,，通過對(duì)這些數(shù)據(jù)進(jìn)行深入分析,，結(jié)果將對(duì)于開發(fā)新型抗生素的活性成分帶來(lái)很大希望。相關(guān)研究成果刊登在了國(guó)際著名雜志PNAS上,。
哺乳動(dòng)物的腸道微生物菌群是由多種多樣的細(xì)菌及其它微生物組成,，人類的腸道也是許多微生物的棲身之地,，在這里，微生物可以或許其生存和繁殖必須的營(yíng)養(yǎng)物質(zhì),。在營(yíng)養(yǎng)物質(zhì)以及碳水化合物豐富,，但是缺乏氧氣的環(huán)境中，許多細(xì)菌進(jìn)化發(fā)展出了一種特殊的代謝形式：混合酸發(fā)酵過程,，這種代謝過程涉及糖分解,，使得糖進(jìn)入腸道成為像甲酸（醋酸或者乳酸）一樣的有機(jī)酸，然后將其排泄掉,。這個(gè)過程為細(xì)菌提供了基本的能量,，而且微環(huán)境也進(jìn)行了土壤酸化的作用，同時(shí)這個(gè)過程也獲益于腸道中的有益細(xì)菌和致病菌,，比如像沙門氏菌一樣的致病菌也從此獲益,。在人類機(jī)體中是沒有混合酸發(fā)酵的，細(xì)菌進(jìn)行此項(xiàng)過程所涉及的分子組分為將來(lái)我們開發(fā)抵御致病菌感染的新型抗生素活性成分提供了基礎(chǔ),。
甲酸鹽（Formate）是混合酸發(fā)酵過程中的中間蛋白質(zhì)成分,，腸道細(xì)菌具有甲酸鹽通道FocA，其實(shí)一種特殊的運(yùn)輸?shù)鞍踪|(zhì),，可以運(yùn)輸甲酸鹽以及甲酸負(fù)離子通過細(xì)菌的細(xì)胞膜。為了研究FocA的更多功能,，研究者將這種蛋白質(zhì)引入到人工生物膜中,，當(dāng)其通過通道進(jìn)行流動(dòng)的時(shí)候，測(cè)定其離子的電流強(qiáng)度,。
為了更精確地得到FocA的運(yùn)輸行為的精確數(shù)據(jù),，研究小組通過通道獲取設(shè)備收集到了其詳細(xì)的信息，當(dāng)環(huán)境中的pH值過低的時(shí)候,，它會(huì)通過繼續(xù)外排酸來(lái)阻止細(xì)菌受到傷害,，研究小組同時(shí)也發(fā)現(xiàn)FocA可以轉(zhuǎn)運(yùn)不同的陰離子，如乙酸離子,、乳酸離子和丙酮酸離子等,，這些都是混合酸發(fā)酵的產(chǎn)物。
FocA對(duì)于整個(gè)過程具有中樞的重要性,，研究結(jié)果將為未來(lái)治療人類腸道疾病的相關(guān)療法提供基礎(chǔ)和建議,。（生物谷Bioon.com）
編譯自：A channel of unexpected significance
doi:10.1073/pnas.1204201109
PMC:
PMID:
The formate channel FocA exports the products of mixed-acid fermentation
Wei Lü, Juan Du, Nikola J. Schwarzer, Elke Gerbig-Smentek, Oliver Einsle, and Susana L. A. Andrade1
Formate is a major metabolite in the anaerobic fermentation of glucose by many enterobacteria. It is translocated across cellular membranes by the pentameric ion channel/transporter FocA that, together with the nitrite channel NirC, forms the formate/nitrite transporter (FNT) family of membrane transport proteins. Here we have carried out an electrophysiological analysis of FocA from Salmonella typhimurium to characterize the channel properties and assess its specificity toward formate and other possible permeating ions. Single-channel currents for formate, hypophosphite and nitrite revealed two mechanistically distinct modes of gating that reflect different types of structural rearrangements in the transport channel of each FocA protomer. Moreover, FocA did not conduct cations or divalent anions, but the chloride anion was identified as further transported species, along with acetate, lactate and pyruvate. Formate, acetate and lactate are major end products of anaerobic mixed-acid fermentation, the pathway where FocA is predominantly required, so that this channel is ideally adapted to act as a multifunctional export protein to prevent their intracellular accumulation. Because of the high degree of conservation in the residues forming the transport channel among FNT family members, the flexibility in conducting multiple molecules is most likely a general feature of these proteins.
