Wei Xingxing, Chan Tsz Ki, Kong Che Tung Derek, Matsuda Yudai
Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR, China.
City University of Hong Kong Shenzhen Research Institute, Shenzhen, Guangdong 518057, China.
J Nat Prod. 2023 Feb 24;86(2):416-422. doi: 10.1021/acs.jnatprod.2c01065. Epub 2023 Jan 30.
The biosynthetic gene cluster of γ-aminobutyric acid (GABA)-containing fungal cyclic heptapeptides unguisins A () and B () was identified in the fungus CBS 115571. In vitro enzymatic reactions and gene deletion experiments revealed that the unguisin pathway involves the alanine racemase UngC to provide d-alanine, which is then accepted by the first adenylation domain of the nonribosomal peptide synthetase (NRPS) UngA. Intriguingly, the hydrolase UngD was found to transform unguisins into previously undescribed linear peptides. Subsequently, heterologous production of these peptides in was achieved, in which we established a methodology to readily introduce a large NRPS gene into the fungal host. Finally, genome mining revealed new unguisin congeners, each containing a (2,3)-β-methylphenylalanine residue.
在真菌CBS 115571中鉴定出了含γ-氨基丁酸（GABA）的真菌环状七肽unguisins A（）和B（）的生物合成基因簇。体外酶促反应和基因缺失实验表明，unguisin生物合成途径涉及丙氨酸消旋酶UngC以提供d-丙氨酸，然后d-丙氨酸被非核糖体肽合成酶（NRPS）UngA的第一个腺苷化结构域接受。有趣的是，发现水解酶UngD可将unguisins转化为先前未描述的线性肽。随后，在中实现了这些肽的异源生产，在此过程中我们建立了一种将大型NRPS基因轻松引入真菌宿主的方法。最后，基因组挖掘揭示了新的unguisin同系物，每个都含有一个（2,3）-β-甲基苯丙氨酸残基。
