Heterologous expression of the cryptic gene cluster and structural revision of maduralactomycin A.
Jan W Schwitalla, Ngoc-Thao-Hien Le, Soohyun Um, Felix Schalk, Mark Brönstrup, Martin Baunach, Christine Beemelmanns
Author Information
Jan W Schwitalla: Chemical Biology of Microbe-Host Interactions, Hans-Knöll Institute (HKI) Beutenbergstraße 11a 07745 Jena Germany. ORCID
Ngoc-Thao-Hien Le: Department of Pharmaceutical Sciences, Natural Products and Food Research and Analysis (NatuRA), University of Antwerp Universiteitsplein 1 B-2610 Antwerp Belgium.
Soohyun Um: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University Incheon 21983 South Korea.
Felix Schalk: Chemical Biology of Microbe-Host Interactions, Hans-Knöll Institute (HKI) Beutenbergstraße 11a 07745 Jena Germany. ORCID
Mark Brönstrup: Department of Chemical Biology, Helmholtz Centre for Infection Research Inhoffenstrasse 7 D-38124 Braunschweig Germany. ORCID
Martin Baunach: Institute of Pharmaceutical Biology, University of Bonn Nussallee 6 53115 Bonn Germany.
Christine Beemelmanns: Chemical Biology of Microbe-Host Interactions, Hans-Knöll Institute (HKI) Beutenbergstraße 11a 07745 Jena Germany. ORCID
After conducting an analysis of the cryptic cluster region and performing transcriptomic studies, an integrative BAC Vector containing the gene sequence was constructed. The heterologous expression of the cluster in J1074 resulted in the production of the angucyclic product, seongomycin, which allowed for the assesment of its antibacterial, antiproliferative, and antiviral activities. Heterologous production was further confirmed by targeted knock-out experiments involving key regulators of the biosynthetic pathways. We were further able to revise the core structure of maduralactomycin A, using a computational approach.
