日前，日本研究人员宣布，他们发现一种酶具有集结“β－赖氨酸”的能力，而这种氨基酸又具有较容易渗透进细胞的构造，如果在一些药物中加入这种酶，就有可能提高其药效。相关研究成果已经发表在新一期《自然—化学生物学》（Nature Chemical Biology）杂志上。
据日本《读卖新闻》网站7月23日报道，日本福井县立大学副教授滨野吉十率领的研究小组发现，“β－赖氨酸”不仅容易渗透进入细胞，而且它对动物没有副作用。研究人员在分析土壤微生物“放线菌”生成抗生素“链丝菌素”的过程中发现，名为“ORF19”的酶能够集结很多“β－赖氨酸”。
研究人员说，如果将这种酶加入到无法渗透进细胞、并对某些患者失去效力的药物中，有可能使其再次发挥作用。比如长期使用抗癌剂时，癌细胞产生耐药性使得药效下降，如果利用酶“ORF19”聚集很多“β－赖氨酸”，可帮助药物渗透进细胞，理论上有可能恢复药效。这种方法或许还有助于研发新药。（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.
