A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.

Significance: Terpenes are generally considered to be plant or fungal metabolites, although a small number of odoriferous terpenes of bacterial origin have been known for many years. Recently, extensive bacterial genome sequencing and bioinformatic analysis of deduced bacterial proteins using a profile based on a hidden Markov model have revealed 262 distinct predicted terpene synthases. Although many of these presumptive terpene synthase genes seem to be silent in their parent microorganisms, controlled expression of these genes in an engineered heterologous Streptomyces host has made it possible to identify the biochemical function of the encoded terpene synthases. Genes encoding such terpene synthases have been shown to be widely distributed in bacteria and represent a fertile source for discovery of new natural products.

Several eubacteria includingEsherichia coliuse an alternative nonmevalonate pathway for the biosynthesis of isopentenyl diphosphate instead of the ubiquitous mevalonate pathway. In the alternative pathway, 2-C-methyl-d-erythritol or its 4-phosphate, which is proposed to be formed from 1-deoxy-d-xylulose 5-phosphate via intramolecular rearrangement followed by reduction process, is one of the biosynthetic precursors of isopentenyl diphosphate. To clone the gene(s) responsible for synthesis of 2-C-methyl-d-erythritol 4-phosphate, we prepared and selectedE. colimutants with an obligatory requirement for 2-C-methylerythritol for growth and survival. All the DNA fragments that complemented the defect in synthesizing 2-C-methyl-d-erythritol 4-phosphate of these mutants contained theyaeMgene, which is located at 4.2 min on the chromosomal map ofE. coli. The gene product showed significant homologies to hypothetical proteins with unknown functions present inHaemophilus influenzae,Synechocystissp. PCC6803,Mycobacterium tuberculosis,Helicobacter pyroli, andBacillus subtilis. The purified recombinantyaeMgene product was overexpressed inE. coliand found to catalyze the formation of 2-C-methyl-d-erythritol 4-phosphate from 1-deoxy-d-xylulose 5-phosphate in the presence of NADPH. Replacement of NADPH with NADH decreased the reaction rate to about 1% of the original rate. The enzyme required Mn²⁺, Co²⁺, or Mg²⁺as well. These data clearly show that theyaeMgene encodes an enzyme, designated 1-deoxy-d-xylulose 5-phosphate reductoisomerase, that synthesizes 2-C-methyl-d-erythritol 4-phosphate from 1-deoxy-d-xylulose 5-phosphate, in a single step by intramolecular rearrangement and reduction and that this gene is responsible for terpenoid biosynthesis inE. coli.

Covering: up to August 2002 This review covers the biosynthesis of the starter units of terpenoids, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) via the nonmevalonate pathway together with a new enzyme involved in the conversion of IPP and DMAPP, i.e. type 2 IPP isomerase. The biosynthesis of terpenoids produced by actinomycetes is also reviewed. 117 references are cited.