Genome sequence of an industrial microorganism Streptomyces avermitilis : Deducing the ability of producing secondary metabolites

Abstract

Streptomyces avermitilis is a soil bacterium that carries out not only a complex morphological differentiation but also the production of secondary metabolites, one of which, avermectin, is commercially important in human and veterinary medicine. The major interest in this genus Streptomyces is the diversity of its production of secondary metabolites as an industrial microorganism. A major factor in its prominence as a producer of the variety of secondary metabolites is its possession of several metabolic pathways for biosynthesis. Here we report sequence analysis of S. avermitilis, covering 99% of its genome. At least 8.7 million base pairs exist in the linear chromosome; this is the largest bacterial genome sequence, and it provides insights into the intrinsic diversity of the production of the secondary metabolites of Streptomyces. Twenty-five kinds of secondary metabolite gene clusters were found in the genome of S. avermitilis. Four of them are concerned with the biosyntheses of melanin pigments, in which two clusters encode tyrosinase and its cofactor, another two encode an ochronotic pigment derived from homogentiginic acid, and another polyketide-derived melanin. The gene clusters for carotenoid and siderophore biosyntheses are composed of seven and five genes, respectively. There are eight kinds of gene clusters for type-I polyketide compound biosyntheses, and two clusters are involved in the biosyntheses of type-II polyketide-derived compounds. Furthermore, a polyketide synthase that resembles phloroglucinol synthase was detected. Eight clusters are involved in the biosyntheses of peptide compounds that are synthesized by nonribosomal peptide synthetases. These secondary metabolite clusters are widely located in the genome but half of them are near both ends of the genome. The total length of these clusters occupies about 6.4% of the genome.S treptomyces is a genus of Gram-positive bacteria that grows in soil, marshes, and coastal marine habitats and forms filamentous mycelium-like eukaryote fungi. Morphological differentiation in Streptomyces involves the formation of a lawn of aerial hyphae on the colony surface that stands up into the air and differentiates into chains of spores (1). This process, unique among Gram-positive bacteria, requires the specialized coordination of metabolism and is more complex than other Gram-positive bacteria. The most interesting property of Streptomyces is its ability to produce secondary metabolites including antibiotics and bioactive compound (2) value in human and veterinary medicine, agriculture, and unique biochemical tools. Structural diversity is observed in these secondary metabolites that encompass not only antibacterial, antifungal, antiviral, and antitumor compounds, but also metabolites with immunosuppressant, antihypertensive, and antihypercholesterolemic properties. Thus, Streptomyces is a rich source of the secondary metabolites in which common intermediates in the cell (amino acids, sugars, fatty acids, terpenes, etc.) are condensed into more complex st...

Evolution of New Function in the GTP Cyclohydrolase II Proteins of Streptomyces coelicolor

“…However, sequence alignments show that the corresponding residue in SCO 6655 is a methionine (Met120). Intriguingly, a Met is present at the analogous position in a homologue of SCO 6655 from S. avermitilis (27) which is localized in a similar gene context. However, a Tyr occupies this position in all GCH II proteins that have been shown to catalyze the formation of APy.…”

Nature as organic chemist

“…96 They inquired whether I would be interested in collaborating to assign the actual biochemical function of the four putative terpene synthase genes that were harbored in the S. avermitilis genome. In fact, it was evident that one of these S. avermitilis terpene synthase genes was a geosmin synthase, 66 while a second corresponded to epi-isozizaene synthase whose function in S. coelicolor we had just established.…”

Simamycin (5′-O-geranyluridine): a new prenylated nucleoside from Streptomyces sp.

“…1 However, it is noteworthy that the number of metabolites isolated is far below the number of gene clusters for secondary metabolite biosynthesis present in the genome of Streptomyces species. 2,3 In our screening for structurally unique or rare secondary metabolites from Streptomyces, we isolated plant hormone-like spiroacetals of polyketide origin, 4 a linear polyketide δ-lactone with antimetastatic property, 5 macrocyclic polyketides with a biosynthetically unprecedented heterocyclic ring structure 6 and methylphenylalanine derivatives with adipocyte differentiation promoting activity. 7 Further attempts to obtain new bioactive compounds from Streptomyces, a soil-derived strain TP-A0872, was chosen for chemical investigation, which led to the isolation of a new geranylated nucleoside, simamycin (1; Figure 1).…”