Cultivated bacteria such as actinomycetes are a highly useful source of biomedically important natural products. However, such ‘talented’ producers represent only a minute fraction of the entire, mostly uncultivated, prokaryotic diversity. The uncultured majority is generally perceived as a large, untapped resource of new drug candidates, but so far it is unknown whether taxa containing talented bacteria indeed exist. Here we report the single-cell- and metagenomics-based discovery of such producers. Two phylotypes of the candidate genus ‘Entotheonella’ with genomes of greater than 9 megabases and multiple, distinct biosynthetic gene clusters co-inhabit the chemically and microbially rich marine sponge Theonella swinhoei. Almost all bioactive polyketides and peptides known from this animal were attributed to a single phylotype. ‘Entotheonella’ spp. are widely distributed in sponges and belong to an environmental taxon proposed here as candidate phylum ‘Tectomicrobia’. The pronounced bioactivities and chemical uniqueness of ‘Entotheonella’ compounds provide significant opportunities for ecological studies and drug discovery.

Covering: up to September 2015 Meroterpenoids are hybrid natural products that partially originate from the terpenoid pathway. The meroterpenoids derived from fungi display quite diverse structures, with a wide range of biological properties. This review summarizes the molecular bases for their biosyntheses, which were recently elucidated with modern techniques, and also discusses the plausible biosynthetic pathways of other related natural products lacking genetic information. (Complementary to the coverage of literature by Geris and Simpson in Nat. Prod. Rep., 2009, 26, 1063–1094.)

Covering: 2002 to 2009 This review covers recent advances in structure and function studies on the chalcone synthase (CHS) superfamily of plant type III polyketide synthases (PKSs), which catalyze iterative decarboxylative condensations of malonyl unit with a CoA-linked starter molecule to produce structurally diverse, pharmaceutically important plant secondary metabolites. The functional diversity and catalytic potential of the type III PKSs are remarkable. Studies on the enzymes are now progressing rapidly; recent crystallographic and site-directed mutagenesis studies have revealed intimate structural details of the enzyme reactions, which enabled the structure-based and precursor-directed engineered biosynthesis of unnatural novel polyketides. The literature of type III PKSs of plant origin published over the last eight years will be reviewed, and is intended to compliment the coverage of the literature by Austin and Noel in Nat. Prod. Rep., 2003, 20, 79–110.

Covering: 2002 to 2006 This review covers recent advances in the chemistry and enzymology of squalene cyclase and oxidosqualene cyclase. The enzymatic cyclizations of squalene and oxidosqualene are the most remarkable steps in the biosynthesis of sterols and triterpenes. The polyenes are converted to various polycyclic triterpenes by different enzyme systems employing only small modification of the active-site. Recent crystallographic and structure-based mutagenesis studies as well as utilization of chemically synthesized active-site probes have begun to reveal intimate structural details of the enzyme-templated cyclization reactions. 126 References are cited.