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.
However, recent studies, which I shall review here, have resulted in progress toward this end.
Polyketide natural products represent a rich source for discovery of new bioactive compounds.
Analysis of the predictions made by all three strategies indicate strong dependence of zinc finger binding specificity on the amino acid propensity and the position of a 3-bp DNA sub-site in the target DNA sequence.
The fact that this lecture is scheduled between lectures on xylanases and amylases perhaps illustrates the common misconception that the ligninolytic system bears a close biochemical similarity to other common biopolymer-degrading microbial systems. It is a most unusual system which has not yet been defined biochemically.Engineering zinc finger protein motifs for specific binding to double-stranded DNA is critical for targeted genome editing.Most existing tools for predicting DNA-binding specificity in zinc fingers are trained on data obtained from naturally occurring proteins, thereby skewing the predictions.In an attempt to elucidate the mechanism of zinc finger protein-DNA interactions, we evaluated and compared three approaches, differing in the amino acid mutations introduced in the Zif-268 parent template, and the mode of binding they try to mimic, i.e., modular and synergistic mode of binding.Comparative evaluation of the three strategies reveals that the synergistic mode of binding appears to mimic the ideal mechanism of DNA-zinc finger protein binding.A distinct group of antimicrobial peptides kills bacteria by interfering with internal cellular functions and without concurrent lytic effects on cell membranes.Here we describe some methods to investigate the mechanisms of action of these antimicrobial peptides.Achieving this goal is hampered by our incomplete understanding of the early events in the female reproductive tract (FRT) during sexual transmission.In particular, how resident HIV- susceptible and non-susceptible cells affect viral replication, and sense and respond to HIV infection, are not well understood.Talk with your doctor and family members or friends about deciding to join a study.To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.Although the upper FRT harbors HIV-susceptible cells, is exposed to semen components, and is infected early in SIV transmission models, it is understudied as a portal of entry for HIV.In cycling women, the endometrium of the upper FRT is extensively remodeled in response to the sex steroids estrogen and progesterone.Polyketides are a large family of bioactive natural products synthesized by polyketide synthase (PKS) enzyme complexes predominantly from acetate and propionate.