1月26日，德国汉斯—克内尔研究所发表新闻公报说，该所研究人员发现，一种“古老”细菌或可用于制造强效抗生素，以有效对抗部分耐药细菌。这项研究成果发表在《自然-化学生物》上。
据介绍，这种细菌存在于意大利石器时代的壁画中，研究人员发现它可产生抗生素Cervimycin，这种抗生素能消灭耐甲氧西林金黄色葡萄球菌等耐药细菌，而当这种“古老”细菌在缺少一种名为CerJ的酶时，能产生一种比Cervimycin更强效的抗生素Cervimycin K。
研究小组负责人克里斯蒂安·赫特韦克说，随着耐药细菌不断增多，找到可对抗这些细菌的强效抗生素已变得“空前急迫”。由于Cervimycin K无法用化学方法获得，他们将探索用生物技术生产这种强效抗生素的可能性。(生物谷 Bioon.com)
doi:10.1038/nchembio.746
PMC:
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.
