Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston Massachusetts 02115, United States.
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States.
ACS Chem Biol. 2021 Jan 15;16(1):6-13. doi: 10.1021/acschembio.0c00673. Epub 2020 Dec 22.
Plasmalogens are vinyl ether-containing lipids produced by mammals and bacteria. The aerobic biosynthetic pathway in eukaryotes and bacteria is known, but the anaerobic pathway has remained a mystery. Here, we describe a two-gene operon (plasmalogen synthase, ) responsible for plasmalogen production in the anaerobic bacterium . While aerobic plasmalogen biosynthesis involves an oxidative conversion of an ether to a vinyl ether, anaerobic plasmalogen biosynthesis uses the reductive conversion of an ester to an aldehyde equivalent. Heterologous expression of the operon in conferred the ability to produce plasmalogens. The operon is predicted to encode a multidomain complex similar to benzoyl-CoA reductase/hydroxylacyl-CoA dehydratase (BCR/HAD) enzymes. Versions of this operon can be found in a wide range of obligate and facultative anaerobic bacteria, including many human gut microbes.
磷脂是哺乳动物和细菌产生的含乙烯醚的脂质。真核生物和细菌中的需氧生物合成途径是已知的,但厌氧途径一直是个谜。在这里,我们描述了一个由两个基因组成的操纵子(磷脂合酶),它负责厌氧细菌中的磷脂生成。虽然需氧磷脂的生物合成涉及醚到乙烯醚的氧化转化,但厌氧磷脂的生物合成使用酯到醛等价物的还原转化。在中异源表达 操纵子赋予了产生磷脂的能力。 操纵子预测编码类似于苯甲酰辅酶 A 还原酶/羟基酰基辅酶 A 脱水酶 (BCR/HAD) 酶的多结构域复合物。该操纵子的版本可以在广泛的专性和兼性厌氧细菌中找到,包括许多人类肠道微生物。