Lazos Orestis, Tosin Manuela, Slusarczyk Adrian L, Boakes Steven, Cortés Jesus, Sidebottom Philip J, Leadlay Peter F
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK.
Chem Biol. 2010 Feb 26;17(2):160-73. doi: 10.1016/j.chembiol.2010.01.011.
The genome of the erythromycin-producing bacterium Saccharopolyspora erythraea contains many orphan secondary metabolite gene clusters including two (nrps3 and nrps5) predicted to govern biosynthesis of nonribosomal peptide-based siderophores. We report here the production by S. erythraea, even under iron-sufficient conditions, of a 2,5-diketopiperazine siderophore candidate we have named erythrochelin. Deletion of the nonribosomal peptide synthetase (NRPS) gene ercD within the nrps5 cluster abolished erythrochelin production. The tetrapeptide backbone of erythrochelin (alpha-N-acetyl-delta-N-acetyl-delta-N-hydroxyornithine-serine-delta-N-hydroxyornithine-delta-N-acetyl-delta-N-hydroxyornithine) suggests an orthodox colinear model for erythrochelin assembly. Curiously, the delta-N-acetyltransferase required for erythrochelin biosynthesis is encoded within a remote NRPS-cluster (nrps1) whose own NRPS contains an inactivating mutation. Disruption of the nrps1 gene mcd abolished erythrochelin biosynthesis, which could then be restored by addition of synthetic L-delta-N-acetyl-delta-N-hydroxyornithine, confirming an unprecedented example of functional crosstalk between nrps clusters.
产生红霉素的细菌糖多孢红霉菌的基因组包含许多孤儿次生代谢物基因簇，其中有两个（nrps3和nrps5）预计可调控基于非核糖体肽的铁载体的生物合成。我们在此报告，即使在铁充足的条件下，糖多孢红霉菌也能产生一种我们命名为红螯菌素的2,5-二酮哌嗪铁载体候选物。nrps5簇内的非核糖体肽合成酶（NRPS）基因ercD的缺失消除了红螯菌素的产生。红螯菌素的四肽主链（α-N-乙酰基-δ-N-乙酰基-δ-N-羟基鸟氨酸-丝氨酸-δ-N-羟基鸟氨酸-δ-N-乙酰基-δ-N-羟基鸟氨酸）提示了红螯菌素组装的正统共线性模型。奇怪的是，红螯菌素生物合成所需的δ-N-乙酰基转移酶是在一个遥远的NRPS簇（nrps1）中编码的，该簇自身的NRPS含有一个失活突变。nrps1基因mcd的破坏消除了红螯菌素的生物合成，然后通过添加合成的L-δ-N-乙酰基-δ-N-羟基鸟氨酸可以恢复，这证实了NRPS簇之间功能串扰的一个前所未有的例子。
