Desferrioxamine B (DFOB) is a siderophore native to Streptomyces pilosus biosynthesised by the DesABCD enzyme cluster as a high affinity Fe(III) chelator. Although DFOB has a long clinical history for the treatment of chronic iron overload, limitations encourage the development of new analogues. This review describes a recent body of work that has used precursor-directed biosynthesis (PDB) to access new DFOB analogues. PDB exploits the native biosynthetic machinery of a producing organism in culture medium augmented with non-native substrates that compete against native substrates during metabolite assembly. The method allows access to analogues of natural products using benign methods, compared to multistep organic synthesis. The disadvantages of PDB are the production of metabolites in low yield and the need to purify complex mixtures. Streptomyces pilosus medium was supplemented with different types of non-native diamine substrates to compete against native 1,5-diaminopentane to generate DFOB analogues containing alkene bonds, fluorine atoms, ether or thioether functional groups, or a disulfide bond. All analogues retained function as Fe(III) chelators and have properties that could broaden the utility of DFOB. These PDB studies have also added knowledge to the understanding of DFOB biosynthesis.

中文翻译：

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使用前体定向生物合成法产生的新特性和新功能的去铁胺B（DFOB）的类似物。

Desferrioxamine B（DFOB）是由链球菌天然产生的铁载体，由DesABCD酶簇作为高亲和力的Fe（III）螯合剂生物合成。尽管DFOB具有治疗慢性铁超负荷的悠久临床历史，但局限性鼓励了新类似物的开发。这篇综述描述了最近的工作，该工作已使用前体定向生物合成（PDB）来访问新的DFOB类似物。PDB利用培养基中生产生物的天然生物合成机制，该培养基中添加了非天然底物，可在代谢产物组装过程中与天然底物竞争。与多步有机合成相比，该方法允许使用良性方法获得天然产物的类似物。PDB的缺点是代谢产物的产量低，并且需要纯化复杂的混合物。在毛霉链霉菌培养基中补充了不同类型的非天然二胺底物，以与天然1，5-二氨基戊烷竞争，生成含有烯烃键，氟原子，醚或硫醚官能团或二硫键的DFOB类似物。所有类似物均具有Fe（III）螯合剂的功能，并具有可以扩大DFOB用途的特性。这些PDB研究也为DFOB生物合成增加了知识。