Re-classification of Streptomyces venezuelae strains and mining secondary metabolite biosynthetic gene clusters

Namil Lee; Mira Choi; Woori Kim; Soonkyu Hwang; Yongjae Lee; Ji Hun Kim; Gahyeon Kim; Hyeseong Kim; Suhyung Cho; Sun Chang Kim; Bernhard Palsson; Kyoung-Soon Jang; Byung-Kwan Cho

doi:10.1016/j.isci.2021.103410

Re-classification of Streptomyces venezuelae strains and mining secondary metabolite biosynthetic gene clusters

iScience. 2021 Nov 9;24(12):103410. doi: 10.1016/j.isci.2021.103410. eCollection 2021 Dec 17.

Authors

Namil Lee^{1

2}, Mira Choi³, Woori Kim^{1

2}, Soonkyu Hwang^{1

2}, Yongjae Lee^{1

2}, Ji Hun Kim^{1

2}, Gahyeon Kim^{1

2}, Hyeseong Kim^{1

2}, Suhyung Cho^{1

2}, Sun Chang Kim¹, Bernhard Palsson^{4

5

6}, Kyoung-Soon Jang^{3

7}, Byung-Kwan Cho^{1

2}

Affiliations

¹ Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
² Innovative Biomaterials Research Center, KI for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
³ Bio-Chemical Analysis Team, Korea Basic Science Institute, Cheongju 28119, Republic of Korea.
⁴ Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
⁵ Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
⁶ Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby 2800, Denmark.
⁷ Division of Bio-Analytical Science, University of Science and Technology, Daejeon 34113, Republic of Korea.

Abstract

Streptomyces species have attracted considerable interest as a reservoir of medically important secondary metabolites, which are even diverse and different between strains. Here, we reassess ten Streptomyces venezuelae strains by presenting the highly resolved classification, using 16S rRNA sequencing, MALDI-TOF MS protein profiling, and whole-genome sequencing. The results revealed that seven of the ten strains were misclassified as S. venezuelae species. Secondary metabolite biosynthetic gene cluster (smBGC) mining and targeted LC-MS/MS based metabolite screening of S. venezuelae and misclassified strains identified in total 59 secondary metabolites production. In addition, a comparison of pyrrolamide-type antibiotic BGCs of four misclassified strains, followed by functional genomics, revealed that athv28 is critical in the synthesis of the anthelvencin precursor, 5-amino-3,4-dihydro-2H-pyrrole-2-carboxylate (ADPC). Our findings illustrate the importance of the accurate classification and better utilization of misclassified Streptomyces strains to discover smBGCs and their secondary metabolite products.

Keywords: Metabolomics; Microbial genomics; Microbiology; Phylogeny.