Elucidating the mechanism of watch internet dating online
We have been investigating the mechanism of fluorinated monomer insertion by three of the six different modules of the PKS involved in erythromycin biosynthesis (6-deoxyerythronolide B synthase, DEBS) to begin understanding the contribution of different steps, such as enzyme acylation, transacylation, C–C bond formation, and chain transfer, to the overall selectivity and efficiency of this process.
In these studies, we observe that inactivation of a -acyltransferase (AT) domain to circumvent its native extender unit preference leads concurrently to a change of mechanism in which chain extension with fluorine-substituted extender units switches largely to an acyl carrier protein (ACP)-independent mode.
Here, we show that fluorine can be inserted site-selectively by an engineered polyketide synthase system via a fluorinated monomer that becomes covalently tethered to the enzyme to complete a canonical reaction cycle.
By increasing the throughput of fluorinated extender units, we can produce multiply fluorinated polyketide products by chemoenzymatic synthesis and target the production of complex structures.
As such, we set out to elucidate the mechanism by which alternative extender units are accepted or rejected in these systems to expand our understanding of the native process of extender unit selection and to define design principles for PKS engineering.
PY - 2010Y1 - 2010N2 - The control of photofragmentation and ionization in a polyatomic molecule has been studied by femtosecond chirped laser pulse excitation and velocity map photoelectron and ion imaging.
Polyketide natural products represent a rich source for discovery of new bioactive compounds.
However, the optimization of polyketide structure for medicinal purposes can be difficult using chemical methods given their complexity.
Site-selective introduction of fluorine into polyketides and other natural products is a particularly interesting area of exploration given the demonstrated effectiveness of fluorine in modulating the behavior of small-molecule therapeutics.In this system, we can amplify single-chain extensions with fluorinated monomers and enable further chain growth to produce polyketide products with multiple fluorine substitutions.), which we attributed to the greater number of enzyme turnovers possible when the extender unit pool is maintained by using an in situ regeneration system for methyl- and fluoromalonyl-Co A (10).