Disease relevance of Soraphen A

• A Sorangium cellulosum (myxobacterium) gene cluster for the biosynthesis of the macrolide antibiotic soraphen A: cloning, characterization, and homology to polyketide synthase genes from actinomycetes [1].
• Heterologous production of the antifungal polyketide antibiotic soraphen A of Sorangium cellulosum So ce26 in Streptomyces lividans [2].

High impact information on Soraphen A

• Here we report the crystal structures of the yeast BC domain, alone and in complex with soraphen A [3].
• Strains carrying the ACC1 suppressor mutation have reduced Acc1 activity in vitro and in vivo, as revealed by enzymatic assays and increased sensitivity to the Acc1-specific inhibitor soraphen A [4].
• The reduced Acc1p activity in hpr1Delta cells, however, did not result in an altered lipid or fatty acid composition of the mutant membranes but rendered cells hypersensitive to soraphen A, an inhibitor of Acc1p [5].
• Characterization of the biosynthetic gene cluster for the antifungal polyketide soraphen A from Sorangium cellulosum So ce26 [6].
• The nucleotide sequence of the soraphen A gene region, including 67,523 bp was determined [6].

Biological context of Soraphen A

• The predicted substrate specificities of the acyltransferase (AT) domains, as well as the reductive loop domains identified within each module, are consistent with expectations from the structure of soraphen A [6].
• In this study, we firstly demonstrate that the integration of a single sor(R) cassette into the P. pastoris genome confers resistance to elevated concentrations of soraphen A [7].
• We have used a genetic approach to localize the target of this drug, employing Saccharomyces cerevisiae as a model organism. we have isolated soraphen A-resistant mutants and found that all of them map at the same genetic locus and exhibit a broad range of semidominant phenotypes [8].

Gene context of Soraphen A

• Taken together these data strongly suggest that the ACC1 gene product is the primary target for soraphen A in vivo [8].

Analytical, diagnostic and therapeutic context of Soraphen A

• Data from genetic crosses of soraphen A-resistant clones with an acc1 mutant revealed that ACC1, coding for acetyl-CoA carboxylase (E.C. 6.4.1.2), is tightly linked to soraphen A resistance [8].
• Cloning, sequence analysis and disruption of the mglA gene involved in swarming motility of Sorangium cellulosum So ce26, a producer of the antifungal polyketide antibiotic soraphen A [9].

References