Department of Pharmaceutical Sciences and Center for Biomolecular Sciences, College of Pharmacy , University of Illinois at Chicago , Chicago , Illinois 60607 , United States.
ACS Synth Biol. 2020 Feb 21;9(2):241-248. doi: 10.1021/acssynbio.9b00438. Epub 2020 Jan 13.
bacteria are an emerging source of natural products with applications in agriculture and medicine. The heterologous expression of biosynthetic gene clusters can streamline natural product discovery; however, production yields with the commonly used host are usually low. Following the current paradigm that one host does not fit all, we aim to develop a host to ultimately tap into the biosynthetic potential of genomes, which can contain up to 27 biosynthetic gene clusters per genome. Because a close phylogenetic relationship is expected to improve the odds of success due to compatible gene expression and precursor supply, we tested sp. FERM BP-3421, a nonpathogenic isolate previously used to produce natural products at industrial scales. We show here that FERM BP-3421 can produce the model lasso peptide capistruin in yields that are at least 65 times and up to 580 times higher than the previously used host.
细菌是天然产物的新兴来源，在农业和医学中有应用。生物合成基因簇的异源表达可以简化天然产物的发现；然而，常用宿主的产量通常较低。根据目前一种宿主不适合所有情况的范式，我们旨在开发一种宿主，最终挖掘基因组的生物合成潜力，每个基因组中可以包含多达 27 个生物合成基因簇。由于密切的系统发育关系有望通过相容的基因表达和前体供应提高成功的几率，我们测试了 sp. FERM BP-3421，这是一种以前用于工业规模生产天然产物的非致病性分离株。我们在这里表明，FERM BP-3421 可以生产模型套索肽 capistruin，产量至少比以前使用的 宿主高 65 倍，高达 580 倍。
