Olano Carlos, Lombó Felipe, Méndez Carmen, Salas José A
Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain.
Metab Eng. 2008 Sep;10(5):281-92. doi: 10.1016/j.ymben.2008.07.001. Epub 2008 Jul 15.
Production of secondary metabolites is a process influenced by several physico-chemical factors including nutrient supply, oxygenation, temperature and pH. These factors have been traditionally controlled and optimized in industrial fermentations in order to enhance metabolite production. In addition, traditional mutagenesis programs have been used by the pharmaceutical industry for strain and production yield improvement. In the last years, the development of recombinant DNA technology has provided new tools for approaching yields improvement by means of genetic manipulation of biosynthetic pathways. These efforts are usually focused in redirecting precursor metabolic fluxes, deregulation of biosynthetic pathways and overexpression of specific enzymes involved in metabolic bottlenecks. In addition, efforts have been made for the heterologous expression of biosynthetic gene clusters in other organisms, looking not only for an increase of production levels but also to speed the process by using rapidly growing and easy to manipulate organisms compared to the producing organism. In this review, we will focus on these genetic approaches as applied to bioactive secondary metabolites produced by actinomycetes.
次级代谢产物的产生是一个受多种物理化学因素影响的过程，这些因素包括营养供应、氧合作用、温度和pH值。传统上，为了提高代谢产物的产量，在工业发酵中会对这些因素进行控制和优化。此外，制药行业一直使用传统的诱变程序来提高菌株和产量。近年来，重组DNA技术的发展为通过对生物合成途径进行基因操作来提高产量提供了新工具。这些努力通常集中在重新引导前体代谢通量、解除生物合成途径的调控以及过表达参与代谢瓶颈的特定酶。此外，人们还致力于在其他生物体中异源表达生物合成基因簇，不仅是为了提高产量，也是为了通过使用与生产生物体相比生长迅速且易于操作的生物体来加快生产过程。在本综述中，我们将重点关注这些应用于放线菌产生的生物活性次级代谢产物的遗传方法。
