Biosynthesis of the Polycyclic System in the Antifungal HSAF and Analogues from Lysobacter enzymogenes.
Biosynthesis of the Polycyclic System in the Antifungal HSAF and Analogues from Lysobacter enzymogenes.
复制标题
抗真菌 HSAF 和产酶溶杆菌类似物中多环系统的生物合成
DOI：
10.1002/anie.201802488
复制
发表时间：
2018-05-22
期刊：
影响因子：
--
通讯作者：
Du L
中科院分区：
文献类型：
--
作者：
Li Y;Wang H;Liu Y;Jiao Y;Li S;Shen Y;Du L
生物防治剂产酶溶杆菌产生多环四酸大环内酰胺（PoTeM），包括抗真菌剂HSAF。为了阐明环状系统的生物合成，我们通过HSAF基因簇的异源表达鉴定了11个具有零、一、二或三环的HSAF前体/类似物。通过一系列组合基因表达和缺失，我们发现OX 3是负责溶杆菌A第一个5元环形成的“看门人”，OX 1和OX 2是负责第二个环形成的，但具有不同的选择性，OX 4是负责6元环形成的。在体外，我们发现OX 4是一种NADPH依赖性酶，催化3-脱羟基阿替酰胺C还原环化形成3-脱羟基HSAF。因此，OX基因的多样性是HSAF家族的结构多样性的基础，HSAF家族是唯一具有特征的PoTeM，其涉及四种氧化还原酶形成循环系统。抗真菌HSAF及其类似物中5-5-6三环系统的0、1、2和3环的生物合成，通过生物合成基因的组合异源表达和体外酶测定揭示。编码NADPH依赖性氧化还原酶的四个OX基因决定了来自革兰氏阴性滑动细菌产酶溶杆菌（Lysobacter enzymogenes）的多环四酸酯大环内酰胺类抗真菌HSAF家族的结构多样性，所述产酶溶杆菌是一种有效的生物防治剂和生物活性产物的多产者。
The biocontrol agent Lysobacter enzymogenes produces polycyclic tetramate macrolactams (PoTeM) including the antifungal HSAF. To elucidate the biosynthesis of the cyclic systems, we identified eleven HSAF precursors/analogues with zero, one, two, or three rings, by heterologous expression of the HSAF gene cluster. Through a series of combinatorial gene expression and deletion, we showed that OX3 is the “gatekeeper” responsible for the first 5-membered ring formation from lysobacterene A, OX1 and OX2 are for the second ring formation but with different selectivity, and OX4 is for the 6-membered ring formation. In vitro, we showed that OX4 is an NADPH-dependent enzyme catalyzing the reductive cyclization of 3-dehydroxy alteramide C to form 3-dehydroxy HSAF. Thus, the multiplicity of OX genes is the basis for the structural diversity of the HSAF family, which is the only characterized PoTeM that involves four redox enzymes in the formation of the cyclic system. Biosynthesis of 0, 1, 2, and 3 Rings of the 5-5-6 Tricyclic System in the Antifungal HSAF and Analogues, as Revealed by Combinatorial Heterologous Expression of the Biosynthetic Genes and in vitro Enzyme assays. Four OX genes that encode NADPH-dependent redox enzymes dictate the structural diversity of the antifungal HSAF family of polycyclic tetramate macrolactams from the Gram-negative gliding bacterium Lysobacter enzymogenes, a potent biocontrol agent and prolific producer of bioactive products.
登录
查看更多内容
DOI：
10.1016/j.bbagen.2016.06.025
发表时间：
2016-10
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Ding Y;Li Y;Li Z;Zhang J;Lu C;Wang H;Shen Y;Du L
通讯作者：
Du L
影响因子：
16.6
作者：
Luo, Yunzi;Huang, Hua;Liang, Jing;Wang, Meng;Lu, Lu;Shao, Zengyi;Cobb, Ryan E.;Zhao, Huimin
通讯作者：
Zhao, Huimin
影响因子：
4.7
作者：
Qi, Yunci;Ding, Edward;Blodgett, Joshua A. V.
通讯作者：
Blodgett, Joshua A. V.
影响因子：
8.4
作者：
Saha S;Zhang W;Zhang G;Zhu Y;Chen Y;Liu W;Yuan C;Zhang Q;Zhang H;Zhang L;Zhang W;Zhang C
通讯作者：
Zhang C
影响因子：
16.6
作者：
Li, Yaoyao;Chen, Haotong;Ding, Yanjiao;Xie, Yunxuan;Wang, Haoxin;Cerny, Ronald L.;Shen, Yuemao;Du, Liangcheng
通讯作者：
Du, Liangcheng