Publication Date:
1995-06-09
Description:
Macrocyclic polyketides exhibit an impressive range of medically useful activities, and there is great interest in manipulating the genes that govern their synthesis. The 6-deoxyerythronolide B synthase (DEBS) of Saccharopolyspora erythraea, which synthesizes the aglycone core of the antibiotic erythromycin A, has been modified by repositioning of a chain-terminating cyclase domain to the carboxyl-terminus of DEBS1, the multienzyme that catalyzes the first two rounds of polyketide chain extension. The resulting mutant markedly accelerates formation of the predicted triketide lactone, compared to a control in which the repositioned domain is inactive. Repositioning of the cyclase should be generally useful for redirecting polyketide synthesis to obtain polyketides of specified chain lengths.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cortes, J -- Wiesmann, K E -- Roberts, G A -- Brown, M J -- Staunton, J -- Leadlay, P F -- New York, N.Y. -- Science. 1995 Jun 9;268(5216):1487-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cambridge Centre for Molecular Recognition, University of Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7770773" target="_blank"〉PubMed〈/a〉
Keywords:
Base Sequence
;
Binding Sites
;
Cloning, Molecular
;
Erythromycin/biosynthesis
;
Genes, Bacterial
;
Genetic Vectors
;
Molecular Sequence Data
;
Multienzyme Complexes/chemistry/genetics/*metabolism
;
*Protein Engineering
;
Saccharopolyspora/*enzymology/genetics
;
Transformation, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
