The development of new herbicides is receiving considerable attention to control weed biotypes resistant to current herbicides. Consequently, new enzymes are always desired as targets for herbicide discovery. 4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is an enzyme engaged in photosynthetic activity and catalyzes the transformation of 4-hydroxyphenylpyruvic acid (HPPA) into homogentisic acid (HGA). HPPD inhibitors constitute a promising area of discovery and development of innovative herbicides with some advantages, including excellent crop selectivity, low application rates, and broad-spectrum weed control. HPPD inhibitors have been investigated for agrochemical interests, and some of them have already been commercialized as herbicides. In this review, we mainly focus on the chemical biology of HPPD, discovery of new potential inhibitors, and strategies for engineering transgenic crops resistant to current HPPD-inhibiting herbicides. The conclusion raises some relevant gaps for future research directions.

ZIF-67 acts as a very efficient catalyst for the cycloaddition of CO2 to epoxides affording cyclic carbonates with high selectivity, without any need for a solvent or a co-catalyst.

The continued propagation of the yeast [PSI(+)] prion requires the molecular chaperone Hsp104 yet in cells engineered to overexpress Hsp104; prion propagation is impaired leading to the rapid appearance of prion-free [psi(-)] cells. The underlying mechanism of prion loss in such cells is unknown but is assumed to be due to the complete dissolution of the prion aggregates by the ATP-dependent disaggregase activity of this chaperone. To further explore the mechanism, we have sought to identify cellular factors required for prion loss in such cells. Sti1p and Cpr7p are co-chaperones that modulate the activity of Hsp70/Ssa and Hsp90 chaperones and bind to the C-terminus of Hsp104. Neither Sti1p nor Cpr7p is necessary for prion propagation but we show that deletion of the STI1 and CPR7 genes leads to a significant reduction in the generation of [psi(-)] cells by Hsp104 overexpression. Deletion of the STI1 and CPR7 genes does not modify the elimination of [PSI(+)] by guanidine hydrochloride, which inhibits the ATPase activity of Hsp104 but does block elimination of [PSI(+)] by overexpression of either an ATPase-defective mutant of Hsp104 (hsp104(K218T/K620T)) or a 'trap' mutant Hsp104 (hsp104(E285Q/E687Q)) that can bind its substrate but can not release it. These results provide support for the hypothesis that [PSI(+)] elimination by Hsp104 overexpression is not simply a consequence of complete dissolution of the prion aggregates but rather is through a mechanism distinct from the remodelling activity of Hsp104.

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We report herein the structure-based design and application of a fluorogenic molecular probe (BChE-FP) specific to butyrylcholinesterase (BChE). This probe was rationally designed by mimicking the native substrate and optimized stepwise by manipulating the steric feature and the reactivity of the designed probe targeting the structural difference of the active pockets of BChE and AChE. The refined probe, BChE-FP, exhibits high specificity toward BChE compared to AChE, producing about 275-fold greater fluorescence enhancement upon the catalysis by BChE. Thus, BChE-FP is a specific BChE probe identified by the structure-based design and it can discriminate BChE from AChE. Furthermore, it has been successfully applied for imaging the endogenous BChE in living cells, as well as BChE inhibitor screening and characterization under physiological conditions.