Centre of Microbial and Plant Genetics, KU Leuven, 3001 Leuven, Belgium.
VIB-KU Leuven Center for Microbiology, Flanders Institute for Biotechnology, 3001 Leuven, Belgium.
Nat Prod Rep. 2024 Jul 17;41(7):1113-1151. doi: 10.1039/d3np00065f.
Covering: up to October 2023Many bioactive natural products are synthesized by microorganisms that are either difficult or impossible to cultivate under laboratory conditions, or that produce only small amounts of the desired compound. By transferring biosynthetic gene clusters (BGCs) into alternative host organisms that are more easily cultured and engineered, larger quantities can be obtained and new analogues with potentially improved biological activity or other desirable properties can be generated. Moreover, expression of cryptic BGCs in a suitable host can facilitate the identification and characterization of novel natural products. Heterologous expression therefore represents a valuable tool for natural product discovery and engineering as it allows the study and manipulation of their biosynthetic pathways in a controlled setting, enabling innovative applications. is a genus of Gram-positive bacteria that is widely used in industrial biotechnology as a host for the production of proteins from diverse origins, including enzymes and vaccines. However, despite numerous successful examples, species remain underexploited as heterologous hosts for the expression of natural product BGCs. Here, we review important advantages that species offer as expression hosts, such as high secretion capacity, natural competence for DNA uptake, and the increasing availability of a wide range of genetic tools for gene expression and strain engineering. We evaluate different strain optimization strategies and other critical factors that have improved the success and efficiency of heterologous natural product biosynthesis in . Finally, future perspectives for using as a heterologous host are discussed, identifying research gaps and promising areas that require further exploration.
截至 2023 年 10 月
许多生物活性天然产物是由微生物合成的，这些微生物要么难以在实验室条件下培养，要么只能产生少量所需的化合物。通过将生物合成基因簇（BGCs）转移到更容易培养和工程改造的替代宿主生物中，可以获得更大的产量，并可以生成具有潜在改善的生物活性或其他理想特性的新类似物。此外，在合适的宿主中表达隐性 BGCs 可以促进新型天然产物的鉴定和表征。因此，异源表达代表了天然产物发现和工程的一种有价值的工具，因为它允许在受控环境中研究和操纵它们的生物合成途径，从而实现创新应用。
是一类革兰氏阳性细菌，广泛应用于工业生物技术，作为生产来自不同来源的蛋白质的宿主，包括酶和疫苗。然而，尽管有许多成功的例子，但 物种仍然作为异源宿主表达天然产物 BGCs 被低估了。在这里，我们回顾了 物种作为表达宿主的重要优势，例如高分泌能力、自然吸收 DNA 的能力，以及越来越多的用于基因表达和菌株工程的广泛遗传工具的可用性。我们评估了不同的菌株优化策略和其他关键因素，这些因素提高了 中异源天然产物生物合成的成功和效率。最后，讨论了未来将 作为异源宿主的前景，确定了需要进一步探索的研究差距和有前途的领域。
