Rodriguez Eduardo, Menzella Hugo G, Gramajo Hugo
Instituto de Biología Molecular y Celular de Rosario (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
Methods Enzymol. 2009;459:339-65. doi: 10.1016/S0076-6879(09)04615-1.
Polyketide natural products are among the most important microbial metabolites in human medicine and are widely used to treat both acute and degenerative diseases. The need to develop new drugs has prompted the idea of using heterologous systems for the expression of polyketide biosynthetic pathways. The basic idea behind this approach is to use heterologous bacterial systems with better growth and genetic characteristics that could support better production of a certain compound than the original host or that could allow the generation of novel analogues through combinatorial biosynthesis. Moreover, these hosts could be used to express "cryptic" secondary metabolic pathways or serve as surrogate hosts in metagenomics experiments in order to find potential new bioactive compounds. In this chapter we discuss recent advances in the heterologous production of polyketides in bacteria and describe some methodological improvements of the systems.
聚酮类天然产物是人类医学中最重要的微生物代谢产物之一,广泛用于治疗急性和退行性疾病。开发新药的需求促使人们提出利用异源系统表达聚酮生物合成途径的想法。这种方法背后的基本思想是使用具有更好生长和遗传特性的异源细菌系统,这些系统能够比原始宿主更好地支持某种化合物的生产,或者能够通过组合生物合成产生新的类似物。此外,这些宿主可用于表达“隐秘的”次级代谢途径,或在宏基因组学实验中用作替代宿主,以寻找潜在的新生物活性化合物。在本章中,我们将讨论细菌中聚酮类化合物异源生产的最新进展,并描述该系统的一些方法学改进。