Department of Chemistry, Queen's University, Kingston, ON K7L 3N6, Canada.
Department of Chemistry, Queen's University, Kingston, ON K7L 3N6, Canada.
Curr Opin Biotechnol. 2021 Jun;69:17-25. doi: 10.1016/j.copbio.2020.10.009. Epub 2020 Dec 6.
As bacteria readily convert simple starting materials into a diverse array of complex molecules with useful bioactivities, these microorganisms and their biosynthetic machinery represent attractive alternatives to traditional chemical syntheses. While the well-documented divergent evolution of biosynthesis has allowed bacteria to explore wide swaths of natural product chemical space, the convergent evolution of these pathways remains a comparably rare phenomenon. The emergence of similar phenotypes within disparate genetic contexts provides a unique opportunity to probe the limitations of natural selection and the predictability and reproducibility of evolution under different constraints. Here, we report several recent examples of functional and structural convergence of bacterial natural products, as well as intra- and inter-domain convergence of bacterial biosynthetic machinery. While the genetic underpinnings of biosynthetic pathway evolution are of fundamental interest, the evolutionary constraints exemplified by phenotypic convergence also have immediate implications for efforts to engineer microorganisms for therapeutic small molecule production.
由于细菌很容易将简单的起始材料转化为具有有用生物活性的各种复杂分子，因此这些微生物及其生物合成机制代表了对传统化学合成的有吸引力的替代方案。虽然生物合成的分化进化得到了充分的证明，使细菌能够探索广泛的天然产物化学空间，但这些途径的趋同进化仍然是一种相对罕见的现象。在不同的遗传背景下出现相似的表型为探究自然选择的局限性以及在不同限制下进化的可预测性和可再现性提供了独特的机会。在这里，我们报告了几个最近的细菌天然产物功能和结构趋同的例子，以及细菌生物合成机制的域内和域间趋同的例子。虽然生物合成途径进化的遗传基础具有根本意义，但表型趋同所体现的进化限制也对为治疗小分子生产而工程化微生物的努力具有直接影响。
