ORCID Profile
0000-0003-4366-3675
Current Organisations
KU Leuven
,
Flanders Insitute for Biotechnology (VIB)
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Publisher: Wiley
Date: 26-10-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7NP00010C
Abstract: Gram-negative bacteria are a rich and underexplored source of antibiotics that are assembled via remarkably erse biosynthetic pathways.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6SC02803A
Abstract: Polyketide synthase reductive chain release and subsequent transamination are key steps in the biosynthesis of polyketide alkaloids in actinobacteria.
Publisher: American Chemical Society (ACS)
Date: 05-06-2017
DOI: 10.1021/JACS.7B03382
Abstract: An antimicrobial activity screen of Burkholderia gladioli BCC0238, a clinical isolate from a cystic fibrosis patient, led to the discovery of gladiolin, a novel macrolide antibiotic with potent activity against Mycobacterium tuberculosis H37Rv. Gladiolin is structurally related to etnangien, a highly unstable antibiotic from Sorangium cellulosum that is also active against Mycobacteria. Like etnangien, gladiolin was found to inhibit RNA polymerase, a validated drug target in M. tuberculosis. However, gladiolin lacks the highly labile hexaene moiety of etnangien and was thus found to possess significantly increased chemical stability. Moreover, gladiolin displayed low mammalian cytotoxicity and good activity against several M. tuberculosis clinical isolates, including four that are resistant to isoniazid and one that is resistant to both isoniazid and rif icin. Overall, these data suggest that gladiolin may represent a useful starting point for the development of novel drugs to tackle multidrug-resistant tuberculosis. The B. gladioli BCC0238 genome was sequenced using Single Molecule Real Time (SMRT) technology. This resulted in four contiguous sequences: two large circular chromosomes and two smaller putative plasmids. Analysis of the chromosome sequences identified 49 putative specialized metabolite biosynthetic gene clusters. One such gene cluster, located on the smaller of the two chromosomes, encodes a trans-acyltransferase (trans-AT) polyketide synthase (PKS) multienzyme that was hypothesized to assemble gladiolin. Insertional inactivation of a gene in this cluster encoding one of the PKS subunits abrogated gladiolin production, confirming that the gene cluster is responsible for biosynthesis of the antibiotic. Comparison of the PKSs responsible for the assembly of gladiolin and etnangien showed that they possess a remarkably similar architecture, obfuscating the biosynthetic mechanisms responsible for most of the structural differences between the two metabolites.
Publisher: American Chemical Society (ACS)
Date: 16-05-2019
DOI: 10.1021/ACSCHEMBIO.9B00270
Abstract: Pentamycin is a polyene antibiotic, registered in Switzerland for the treatment of vaginal candidiasis, trichomoniasis, and mixed infections. Chemical instability has hindered its widespread application and development as a drug. Here, we report the identification of Streptomyces sp. S816, isolated from Philippine mangrove soil, as a pentamycin producer. Genome sequence analysis identified the putative pentamycin biosynthetic gene cluster, which shows a high degree of similarity to the gene cluster responsible for filipin III biosynthesis. The ptnJ gene, which is absent from the filipin III biosynthetic gene cluster, was shown to encode a cytochrome P450 capable of converting filipin III to pentamycin. This confirms that the cluster directs pentamycin biosynthesis, paving the way for biosynthetic engineering approaches to the production of pentamycin analogues. Several other Streptomyces genomes were found to contain ptnJ orthologues clustered with genes encoding polyketide synthases that appear to have similar architectures to those responsible for the assembly of filipin III and pentamycin, suggesting pentamycin production may be common in Streptomyces species.
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4SC01927J
Abstract: Zeamine assembly involves nonribosomal peptide, polyketide and polyunsaturated fatty acid-like biosynthetic pathways.
Publisher: Springer Science and Business Media LLC
Date: 23-09-2019
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C8SC04897E
Abstract: Fungus-associated Burkholderia gladioli bacteria use a unique ‘dual-priming’ nonribosomal peptide synthetase to assemble icosalide A1.
Publisher: Springer Science and Business Media LLC
Date: 23-09-2019
Publisher: Wiley
Date: 26-10-2020
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Joleen Masschelein.