Engineering the FK228 biosynthetic gene clusters for high-yield production
- 1State Key Laboratory of Microbial Technology, Shandong University
- 2NHC Key Lab of Reproduction Regulation, Shanghai Engineering Research Center of Reproductive Health Drugs and Devices, Shanghai Institute for Biomedical and Pharmaceutical Technologies
Abstract
FK228 (romidepsin) is a potent HDAC inhibitor; however, its clinical application is severely constrained by low natural yields and the genetic intractability of its native producer. Here, we leveraged the established Burkholderia chassis KOGC1 to develop a high-performance platform for FK228 production. Through systematic fermentation optimization, we addressed major production constraints including potential end-product toxicity and precursor supply. Specifically, the integration of XAD-16 resin adsorption together with the combined feeding of key amino acids (cysteine, valine, and threonine) elevated the titer to 743.5 mg/L. Subsequent refactoring of the biosynthetic gene cluster and promoter engineering further increased the titer to 1109.4 mg/L. Furthermore, the engineered strain exhibited remarkable genetic stability over five generations without antibiotic selection, which may help address a key barrier to future scale-up. Overall, this study establishes a highly productive laboratory-scale FK228 biosynthetic platform, providing a foundation for future process development of this important therapeutic agent.
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BibTeX
@article{wang2026engineering,
title = {{Engineering the FK228 biosynthetic gene clusters for high-yield production}},
author = {Maoqin Wang and Xuexin Jia and Yunling Zhang and Junchi Ma and Youming Zhang and Jun Fu and Ruijuan Li},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1933794},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1933794/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Engineering the FK228 biosynthetic gene clusters for high-yield production
AU - Maoqin Wang
AU - Xuexin Jia
AU - Yunling Zhang
AU - Junchi Ma
AU - Youming Zhang
AU - Jun Fu
AU - Ruijuan Li
PY - 2026
DA - 2026/10/15
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1933794
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1933794/full
AB - FK228 (romidepsin) is a potent HDAC inhibitor; however, its clinical application is severely constrained by low natural yields and the genetic intractability of its native producer. Here, we leveraged the established Burkholderia chassis KOGC1 to develop a high-performance platform for FK228 production. Through systematic fermentation optimization, we addressed major production constraints including potential end-product toxicity and precursor supply. Specifically, the integration of XAD-16 resin adsorption together with the combined feeding of key amino acids (cysteine, valine, and threonine) elevated the titer to 743.5 mg/L. Subsequent refactoring of the biosynthetic gene cluster and promoter engineering further increased the titer to 1109.4 mg/L. Furthermore, the engineered strain exhibited remarkable genetic stability over five generations without antibiotic selection, which may help address a key barrier to future scale-up. Overall, this study establishes a highly productive laboratory-scale FK228 biosynthetic platform, providing a foundation for future process development of this important therapeutic agent.
SN - 1664-302X
ER -