No abstract

The enterocin biosynthesis gene cluster represents the most versatile type II PKS system investigated to date. A large series of divergent metabolites are naturally generated from the single biochemical pathway, which has several metabolic options for creating structural diversity. The absence of cyclase and aromatase gene products and the involvement of an oxygenase-catalyzed Favorskii-like rearrangement provide insight into the observed spontaneity of this pathway. This system provides the foundation for engineering hybrid expression sets in the generation of structurally novel compounds for use in drug discovery.

Although phenylpropanoids and flavonoids are common plant natural products, these major classes of biologically active secondary metabolites are largely absent from bacteria. The ubiquitous plant enzymes phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) are key biosynthetic catalysts in phenylpropanoid and flavonoid assembly, respectively. Until recently, few bacterial counterparts were known, thus reflecting the dearth of these plant natural products in bacteria. This review highlights our progress on the biochemical and genetic characterization of recently identified streptomycete biosynthetic pathways to benzoic acid and type III polyketide synthase (PKS)-derived products. The sediment-derived bacterium "Streptomyces maritimus" produces benzoyl-CoA in a plant-like manner from phenylalanine involving a PAL-mediated reaction through cinnamic acid during the biosynthesis of the polyketide antibiotic enterocin. All but one of the genes encoding benzoyl-CoA biosynthesis in "S. maritimus" have been cloned, sequenced, and inactivated, providing a model for benzoate biosynthesis not only in this bacterium, but in plants where benzoic acid is an important constituent of many products. The recent discovery that bacteria harbor homodimeric PKSs belonging to the plant CHS superfamily of condensing enzymes has further linked the biosynthetic capabilities of plants and bacteria. A bioinformatics approach led to the prediction that the model actinomycete Streptomyces coelicolor A3(2) contains up to three type III PKSs. Biochemical analysis of one of the recombinant type III PKSs from S. coelicolor demonstrated activity as a 1,3,6,8-tetrahydroxynaphthalene synthase (THNS). A homology model of THNS based upon the known three-dimensional structure of CHS was constructed to explore the structural and mechanistic details of this new subclass of bacterial PKSs.

Vaccinium have been identified [1], and there are 18 identified species in the flora of British Columbia, Canada [2]. Vaccinium macrocarpon Aiton, commonly known as "large cranberry", is a diploid (2 n = 24) native of the northeastern USA, bred through agricultural selection and grown as a commercial crop in the lower mainland of British Columbia [3]. Vaccinium oxycoccos L., (2 n = 24, 48, 72) commonly known as "small cranberry" or "bog cranberry", and Vaccinium vitis-idaea L., (2 n = 24) commonly known as "rock cranberry" or "northern mountain cranberry" in North America and "lingonberry" in Europe, are all found in native populations across North America and Europe including widespread natural populations in the coastal and mountainous regions of British Columbia [1, 2, 4-6]. Cranberries have had important roles in the traditional health and culture of indigenous people across North America as well as modern uses in the natural health products industry. Although Vaccinium vitis-idaea L. is taxonomically closer to the bilberry, Vaccinium myrtillus L., than it is to the cranberry species, in traditional practices, the natives essentially treated and used V. vitis-idaea in the same way as the V. oxycoccos and V. macrocarpon species [7-9]. Traditionally, V. macrocarpon berries were gathered from August through the fall, even when still unripe, allowed to ripen and then eaten either fresh or cooked [8]. Moerman reported the use of wild V. macrocarpon by the Algonquin, Chippewa, Ojibwa, and Iroquois in baked, dried, and raw foods, mixed with corn breads, and sold or traded for other commodities [10]. Several uses of V. oxycoccos by the indigenous people of northern Canada have been described including consumption of fresh berries, berries