A gene cluster encoding resistomycin biosynthesis in Streptomyces resistomycificus; exploring polyketide cyclization beyond linear and angucyclic patterns.
Resistomycin is a pentacyclic polyketide metabolite of Streptomyces resistomycificus that exhibits a variety of pharmacologically relevant properties. While virtually all bacterial aromatic polyketides can be grouped into linear and angular polyphenols, resistomycin has a unique "discoid" ring system. We have successfully identified the entire gene cluster encoding resistomycin biosynthesis by heterologously expressing a pooled cosmid library and screening for the fluorescence of the metabolite produced. The rem gene cluster exhibits several unusual features of the type II PKS involved, most remarkably a putative MCAT with highest homology to AT domains from modular PKSs. In addition, we provide the first insight into the molecular basis of a unique mode of cyclization giving rise to a discoid polyketide.
Jakobi
Kathrin
K
Hans-Knöll-Institute for Natural Products Research, Department of Bioorganic Synthesis, Beutenbergstrasse 11a, 07745 Jena, Germany.
Hertweck
Christian
C
D001580:Benzopyrenes / Q000378:metabolism*; D003360:Cosmids / Q000235:genetics; D003500:Cyclization; D005453:Fluorescence; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D010957:Plasmids / Q000235:genetics; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism
D001580:Benzopyrenes; D009097:Multienzyme Complexes; C018379:resistomycin