This paper focuses primarily on the means by which biochemical information can be used to identify enzymes which, upon inhibition, produce lethal phenotypes and the enzyme inhibitor design strategies that have the highest probability of not only inhibiting the enzyme but also translating that inhibition into herbicidal efficacy. The identification of an exquisitely lethal target site is the key initial component to this approach and has often been one of the most difficult steps because the attributes of a lethal site have, at best, been ill-defined. An examination of the characteristics of known targets provides some insight as to the definition of a lethal target. Recently, antisense RNA suppression of enzyme translation has been used to determine the extent of inhibition required for toxicity and offers potential as a strategy for identifying lethal target sites. After identification of a lethal target, detailed knowledge of the enzyme's chemical and kinetic mechanism as well as the protein's structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. The advantages and disadvantages of a given type with respect to in vivo efficacy as well as the probability of herbicide resistance development will be discussed.

Photosystem II (PS II) inhibitors halt electron flow within the photosynthetic electron transport chain, thereby leading to increased oxidative stress. As a result, their addition to mesotrione, which inhibits carotenoid biosynthesis by inhibition of the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD), is complementary. Field and greenhouse experiments were conducted in 2002 and 2003 to investigate the joint action of POST mesotrione plus PS II inhibitor herbicide combinations. The joint action of mesotrione plus PS II inhibitors was investigated across five plant species, three PS II inhibitors, and two moisture environments to determine their influence on the joint action response. Rates of mesotrione evaluated ranged from 4.4 to 87.6 g ai/ha alone and in combination with reduced rates of atrazine, bromoxynil, and metribuzin. In the field, all combinations of mesotrione at 8.8, 17.5, and 35.0 g/ha plus atrazine, bromoxynil, or metribuzin were synergistic for necrosis 6 d after treatment (DAT) on sunflower. Addition of atrazine at 280 g/ha to mesotrione at 8.8 g/ha increased velvetleaf leaf necrosis by 18 to 47%. In the greenhouse, the addition of bromoxynil at 70 g/ha to mesotrione at 17.5 g/ha increased leaf necrosis by 23 to 34% and biomass reduction by 38 to 47%. Synergism on Palmer amaranth occurred similarly under both normal and dry moisture environments at application. Plant height at application was found to influence detection of synergism on the whole-plant level.