生物碱类天然产物通常具有复杂多样的化学结构和广泛的生物活性，因此备受生物学、化学、药学领域研究者的关注。微生物是仅次于植物的生物碱类天然产物重要来源，微生物尤其是放线菌产生的众多次生代谢产物中，也包括很多生物碱。对放线菌来源生物碱的骨架结构和药效基团生物合成研究，不仅能够丰富人们对天然产物结构形成原理的理解，还可以为运用合成生物学技术人工合成此类化合物提供重要的遗传元件。本文从模块化生物合成和非模块化生物合成两种方式，综述放线菌来源生物碱的生物合成基因簇、途径及其酶催化反应过程。
Alkaloid natural products generally have complex and diverse chemical structures and exhibit a wide range of biological activities, and therefore are of great interest to biologists, chemists, and pharmacists. Apart from plants, microorganisms have been identified as the most important source of natural alkaloids. Microorganisms, especially actinomycetes, produce many secondary metabolites including alkaloids. Studies on the biosynthesis of skeletons and pharmacophores of alkaloids produced by actinomycetes not only enrich our understanding of the biosynthetic mechanism of natural products, but also provide important genetic elements in order to generate these compounds or the derivatives by designed and man-made synthetic pathways in heterologous host using synthetic biology. This review provides a summary of recent research advances in elucidating the biosynthesis of alkaloids from actinomycetes. The detailed biochemical mechanisms have been summarized in modular biosynthetic machineries and non-modular enzymatic systems, respectively.
Contents
1 Introduction
2 Modular biosynthesis of alkaloids
2.1 Diketopiperazine alkaloids
2.2 Pyrrolobenzodiazepines
2.3 Tetrahydroisoquinolines
2.4 Maremycins family
3 Non-modular biosynthesis of alkaloids
3.1 Streptonigrinoids
3.2 Spirocycloproprane family
3.3 Indolocarbazole alkaloids
3.4 Aminobenzoquinone-aziridine alkaloids
4 Conclusion and outlook
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