| Title: |
High-Yield Production of Herbicidal Thaxtomins and Thaxtomin Analogs in a Nonpathogenic Streptomyces Strain |
| Authors: |
Jiang, Guangde; Zhang, Yucheng; Powell, Magan M.; Zhang, Peilan; Zuo, Ran; Zhang, Yi; Kallifidas, Dimitris; Tieu, Albert M.; Luesch, Hendrik; Loria, Rosemary; Ding, Yousong |
| Contributors: |
Parales, Rebecca E.; NHMFL; DOD | USAF | AFMC | Air Force Office of Scientific Research |
| Source: |
Applied and Environmental Microbiology ; volume 84, issue 11 ; ISSN 0099-2240 1098-5336 |
| Publisher Information: |
American Society for Microbiology |
| Publication Year: |
2018 |
| Description: |
Thaxtomins are virulence factors of most plant-pathogenic Streptomyces strains. Due to their potent herbicidal activity, attractive environmental compatibility, and inherent biodegradability, thaxtomins are key active ingredients of bioherbicides approved by the U.S. Environmental Protection Agency. However, the low yield of thaxtomins in native Streptomyces producers limits their wide agricultural applications. Here, we describe the high-yield production of thaxtomins in a heterologous host. The thaxtomin gene cluster from S. scabiei 87.22 was cloned and expressed in S. albus J1074 after chromosomal integration. The production of thaxtomins and nitrotryptophan analogs was observed using liquid chromatography-mass spectrometry (LC-MS) analysis. When the engineered S. albus J1074 was cultured in the minimal medium Thx defined medium supplemented with 1% cellobiose (TDMc), the yield of the most abundant and herbicidal analog, thaxtomin A, was 10 times higher than that in S. scabiei 87.22, and optimization of the medium resulted in the highest yield of thaxtomin analogs at about 222 mg/liter. Further engineering of the thaxtomin biosynthetic gene cluster through gene deletion led to the production of multiple biosynthetic intermediates important to the chemical synthesis of new analogs. Additionally, the versatility of the thaxtomin biosynthetic system in S. albus J1074 was capitalized on to produce one unnatural fluorinated analog, 5-fluoro-thaxtomin A (5-F-thaxtomin A), whose structure was elucidated by a combination of MS and one-dimensional (1D) and 2D nuclear magnetic resonance (NMR) analyses. Natural and unnatural thaxtomins demonstrated potent herbicidal activity in radish seedling assays. These results indicated that S. albus J1074 has the potential to produce thaxtomins and analogs thereof with high yield, fostering their agricultural applications. IMPORTANCE Thaxtomins are agriculturally valuable herbicidal natural products, but the productivity of native producers is limiting. Heterologous ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1128/aem.00164-18 |
| DOI: |
10.1128/AEM.00164-18 |
| Availability: |
https://doi.org/10.1128/aem.00164-18; https://journals.asm.org/doi/pdf/10.1128/AEM.00164-18 |
| Rights: |
https://journals.asm.org/non-commercial-tdm-license |
| Accession Number: |
edsbas.BB176C70 |
| Database: |
BASE |