Hydroxylation modulates the activity of many pharmacological biomolecules. It can be integral to the basic biosynthetic factory or result from tailoring steps. For anti-MRSA antibiotic mupirocin, removal of C8-hydroxyl late in biosynthesis gives the active pseudomonic acid A. An extra hydroxylation, at C4, occurs in the related antibiotic thiomarinol A. We report here that putative non-heme-iron(II)/α-ketoglutarate-dependent dioxygenase TmuB, from the thiomarinol cluster, 4-hydroxylates various pseudomonic acids while C8-OH, and other substituents around the pyran ring, block enzyme action but not substrate binding. Molecular modelling suggested a basis for selectivity but mutational studies showed limited ability to rationally modify TmuB ...
SummaryAn artificial operon was synthesized, consisting of the genes for chorismate pyruvate-lyase o...
Mupirocin, a clinically important antibiotic produced via a <i>trans</i>-AT Type I polyketide syntha...
Organic chemistry is a valuable tool for studying enzyme mechanisms. Upon incubation with a specific...
Addition or removal of hydroxyl groups modulates the activity of many pharmacologically active biomo...
SummaryMupirocin, a polyketide-derived antibiotic from Pseudomonas fluorescens NCIMB10586, is a mixt...
AbstractThe polyketide antibiotic mupirocin (pseudomonic acid) produced by Pseudomonas fluorescens N...
There is a clear and well-established need for new antibiotics. The biosynthesis of the antibiotic m...
Background Understanding how complex antibiotics are synthesised by their producer bacteria is esse...
The modular polyketide synthase responsible for biosynthesis of the antibiotic mupirocin occupies 75...
This work was funded by BBSRC grants BB/I014373/1 and BB/I014039/1, by BBSRC and EPSRC through the B...
Biosynthetic steps in the mupirocin (pseudomonic acids) biosynthetic pathway of \(Pseudomonas\) \(fl...
Thiomarinol is a naturally occurring double-headed antibiotic that is highly potent against methicil...
Polyketide synthases (PKS) are enzyme complexes that synthesise many natural products of medicinal i...
Natural products made by bacteria have long been utilized as inspiration for antibiotic treatments. ...
The mupirocin biosynthetic pathway belongs to the trans-AT group in which acyltransferase (AT) activ...
SummaryAn artificial operon was synthesized, consisting of the genes for chorismate pyruvate-lyase o...
Mupirocin, a clinically important antibiotic produced via a <i>trans</i>-AT Type I polyketide syntha...
Organic chemistry is a valuable tool for studying enzyme mechanisms. Upon incubation with a specific...
Addition or removal of hydroxyl groups modulates the activity of many pharmacologically active biomo...
SummaryMupirocin, a polyketide-derived antibiotic from Pseudomonas fluorescens NCIMB10586, is a mixt...
AbstractThe polyketide antibiotic mupirocin (pseudomonic acid) produced by Pseudomonas fluorescens N...
There is a clear and well-established need for new antibiotics. The biosynthesis of the antibiotic m...
Background Understanding how complex antibiotics are synthesised by their producer bacteria is esse...
The modular polyketide synthase responsible for biosynthesis of the antibiotic mupirocin occupies 75...
This work was funded by BBSRC grants BB/I014373/1 and BB/I014039/1, by BBSRC and EPSRC through the B...
Biosynthetic steps in the mupirocin (pseudomonic acids) biosynthetic pathway of \(Pseudomonas\) \(fl...
Thiomarinol is a naturally occurring double-headed antibiotic that is highly potent against methicil...
Polyketide synthases (PKS) are enzyme complexes that synthesise many natural products of medicinal i...
Natural products made by bacteria have long been utilized as inspiration for antibiotic treatments. ...
The mupirocin biosynthetic pathway belongs to the trans-AT group in which acyltransferase (AT) activ...
SummaryAn artificial operon was synthesized, consisting of the genes for chorismate pyruvate-lyase o...
Mupirocin, a clinically important antibiotic produced via a <i>trans</i>-AT Type I polyketide syntha...
Organic chemistry is a valuable tool for studying enzyme mechanisms. Upon incubation with a specific...