日前,，日本研究人員宣布，他們發(fā)現(xiàn)一種酶具有集結(jié)“β－賴氨酸”的能力,，而這種氨基酸又具有較容易滲透進細胞的構(gòu)造,，如果在一些藥物中加入這種酶,，就有可能提高其藥效。相關(guān)研究成果已經(jīng)發(fā)表在新一期《自然—化學(xué)生物學(xué)》（Nature Chemical Biology）雜志上,。
據(jù)日本《讀賣新聞》網(wǎng)站7月23日報道,，日本福井縣立大學(xué)副教授濱野吉十率領(lǐng)的研究小組發(fā)現(xiàn)，“β－賴氨酸”不僅容易滲透進入細胞,，而且它對動物沒有副作用,。研究人員在分析土壤微生物“放線菌”生成抗生素“鏈絲菌素”的過程中發(fā)現(xiàn)，名為“ORF19”的酶能夠集結(jié)很多“β－賴氨酸”,。
研究人員說,，如果將這種酶加入到無法滲透進細胞、并對某些患者失去效力的藥物中,，有可能使其再次發(fā)揮作用,。比如長期使用抗癌劑時，癌細胞產(chǎn)生耐藥性使得藥效下降,，如果利用酶“ORF19”聚集很多“β－賴氨酸”,，可幫助藥物滲透進細胞，理論上有可能恢復(fù)藥效,。這種方法或許還有助于研發(fā)新藥,。（生物谷Bioon.com）
doi:10.1038/nchembio.1040
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A stand-alone adenylation domain forms amide bonds in streptothricin biosynthesis
Chitose Maruyama,1 Junya Toyoda,1 Yasuo Kato,2 Miho Izumikawa,3 Motoki Takagi,3 Kazuo Shin-ya,4 Hajime Katano,1 Takashi Utagawa1 & Yoshimitsu Hamano1
The streptothricin (ST) antibiotics, produced by Streptomyces bacteria, contain L-β-lysine ((3S)-3,6-diaminohexanoic acid) oligopeptides as pendant chains. Here we describe three unusual nonribosomal peptide synthetases (NRPSs) involved in ST biosynthesis: ORF 5 (a stand-alone adenylation (A) domain), ORF 18 (containing thiolation (T) and condensation (C) domains) and ORF 19 (a stand-alone A domain). We demonstrate that ST biosynthesis begins with adenylation of L-β-lysine by ORF 5, followed by transfer to the T domain of ORF 18. In contrast, L-β-lysine molecules adenylated by ORF 19 are used to elongate an L-β-lysine peptide chain on ORF 18, a reaction unexpectedly catalyzed by ORF 19 itself. Finally, the C domain of ORF 18 catalyzes the condensation of L-β-lysine oligopeptides covalently bound to ORF 18 with a freely diffusible intermediate to release the ST products. These results highlight an unusual activity for an A domain and unique mechanisms of crosstalk within NRPS machinery.
