1月26日，德國(guó)漢斯—克內(nèi)爾研究所發(fā)表新聞公報(bào)說(shuō),，該所研究人員發(fā)現(xiàn),，一種“古老”細(xì)菌或可用于制造強(qiáng)效抗生素，以有效對(duì)抗部分耐藥細(xì)菌,。這項(xiàng)研究成果發(fā)表在《自然-化學(xué)生物》上,。
據(jù)介紹，這種細(xì)菌存在于意大利石器時(shí)代的壁畫中,，研究人員發(fā)現(xiàn)它可產(chǎn)生抗生素Cervimycin,，這種抗生素能消滅耐甲氧西林金黃色葡萄球菌等耐藥細(xì)菌，而當(dāng)這種“古老”細(xì)菌在缺少一種名為CerJ的酶時(shí),，能產(chǎn)生一種比Cervimycin更強(qiáng)效的抗生素Cervimycin K,。
研究小組負(fù)責(zé)人克里斯蒂安·赫特韋克說(shuō)，隨著耐藥細(xì)菌不斷增多,，找到可對(duì)抗這些細(xì)菌的強(qiáng)效抗生素已變得“空前急迫”,。由于Cervimycin K無(wú)法用化學(xué)方法獲得，他們將探索用生物技術(shù)生產(chǎn)這種強(qiáng)效抗生素的可能性,。(生物谷 Bioon.com)
doi:10.1038/nchembio.746
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PMID:
A ketosynthase homolog uses malonyl units to form esters in cervimycin biosynthesis
Tom Bretschneider, Georg Zocher, Michelle Unger, Kirstin Scherlach, Thilo Stehle, & Christian Hertweck,
Ketosynthases produce the carbon backbones of a vast number of biologically active polyketides by catalyzing Claisen condensations of activated acyl and malonyl building blocks. Here we report that a ketosynthase homolog from Streptomyces tendae, CerJ, unexpectedly forms malonyl esters during the biosynthesis of cervimycin, a glycoside antibiotic against methicillin-resistant Staphylococcus aureus (MRSA). Deletion of cerJ yielded a substantially more active cervimycin variant lacking the malonyl side chain, and in vitro biotransformations revealed that CerJ is capable of transferring malonyl, methylmalonyl and dimethylmalonyl units onto the glycoside. According to phylogenetic analyses and elucidation of the crystal structure, CerJ is functionally and structurally positioned between the ketosynthase catalyzing Claisen condensations and acyl-ACP shuttles, and it features a noncanonical catalytic triad. Site-directed mutagenesis and structures of CerJ in complex with substrates not only allowed us to establish a model for the reaction mechanism but also provided insights into the evolution of this important subclass of the thiolase superfamily.
