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在工程化的 Lysobacter enzymogenes 菌株中生产抗耐甲氧西林金黄色葡萄球菌抗生素 WAP-8294A 的系统优化。

Systematic optimization for production of the anti-MRSA antibiotics WAP-8294A in an engineered strain of Lysobacter enzymogenes.

机构信息

Department of Biotechnology, Jiangnan University, Wuxi, Jiangsu, 214122, China.

Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA.

出版信息

Microb Biotechnol. 2019 Nov;12(6):1430-1440. doi: 10.1111/1751-7915.13484. Epub 2019 Sep 14.

DOI:10.1111/1751-7915.13484
PMID:31520522
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6801147/
Abstract

WAP-8294A is a group of cyclic lipodepsipeptides and considered as the first-in-class new chemical entity with potent activity against methicillin-resistant Staphylococcus aureus. One of the roadblocks in developing the WAP-8294A antibiotics is the very low yield in Lysobacter. Here, we carried out a systematic investigation of the nutritional and environmental conditions in an engineered L. enzymogenes strain for the optimal production of WAP-8294A. We developed an activity-based simple method for quick screening of various factors, which enabled us to optimize the culture conditions. With the method, we were able to improve the WAP-8294A yield by 10-fold in small-scale cultures and approximately 15-fold in scale-up fermentation. Additionally, we found the ratio of WAP-8294A2 to WAP-8294A1 in the strains could be manipulated through medium optimization. The development of a practical method for yield improvement in Lysobacter will facilitate the ongoing basic research and clinical studies to develop WAP-8294A into true therapeutics.

摘要

WAP-8294A 是一组环状脂肽类化合物，被认为是具有抗耐甲氧西林金黄色葡萄球菌（MRSA）活性的一类新型化学实体。在开发 WAP-8294A 抗生素的过程中，其中一个障碍是 Lysobacter 中的产量非常低。在这里，我们对工程化的 L. enzymogenes 菌株进行了系统的营养和环境条件研究，以获得最佳的 WAP-8294A 产量。我们开发了一种基于活性的简单方法，用于快速筛选各种因素，使我们能够优化培养条件。使用该方法，我们能够在小规模培养中使 WAP-8294A 的产量提高 10 倍，在放大发酵中提高约 15 倍。此外，我们发现通过培养基优化可以操纵菌株中 WAP-8294A2 与 WAP-8294A1 的比例。开发一种用于提高 Lysobacter 产量的实用方法将有助于正在进行的基础研究和临床研究，将 WAP-8294A 开发成真正的治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/2b59babf3b78/MBT2-12-1430-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/07432e9c72eb/MBT2-12-1430-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/7f9f704e0103/MBT2-12-1430-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/842da8a83fba/MBT2-12-1430-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/e464d7eae04c/MBT2-12-1430-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/ba31d217b816/MBT2-12-1430-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/a2c6e4507052/MBT2-12-1430-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/2b59babf3b78/MBT2-12-1430-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/07432e9c72eb/MBT2-12-1430-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/7f9f704e0103/MBT2-12-1430-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/842da8a83fba/MBT2-12-1430-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/e464d7eae04c/MBT2-12-1430-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/ba31d217b816/MBT2-12-1430-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/a2c6e4507052/MBT2-12-1430-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f87/6801147/2b59babf3b78/MBT2-12-1430-g007.jpg

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