Diterpenoids from Streptomyces: Structures, Biosyntheses and Bioactivities

Abstract

Bacteria, especially Streptomyces spp., have emerged as a rich source for natural diterpenoids with diverse structures and broad bioactivities. Here, we review diterpenoids biosynthesized by Streptomyces, with an emphasis on their structures, biosyntheses, and bioactivities. Although diterpenoids from Streptomyces are relatively rare compared to those from plants and fungi, their novel skeletons, biosyntheses and bioactivities present opportunities for discovering new drugs, enzyme mechanisms, and applications in biocatalysis and metabolic pathway engineering.

Genome-Driven Discovery of Antiviral Atralabdans A–C from the Soil-Dwelling Streptomyces atratus

“…Then, GGPP is converted to a (+) copalyl diphosphate under the catalysis of AtrB. AtrD dephosphorylates the (+) copalyl diphosphate, yielding a labdane-type bicyclic diterpene, labda-8(17),12,14-triene, that is subsequently hydroxylated at C7 by AtrC to form raimonol . AtrE oxidizes raimonol, creating an aldehyde group at C10 to produce labdanmycin A. Labdanmycin A undergoes a reaction akin to aldol condensation under acidic conditions.…”

“…Li observed that most diterpenes tapped through genome mining in streptomycetes exhibit novel skeletons, and the activation and exploration of the terpenoid gene clusters within streptomycetes holds the potential for discovery of novel terpenoids. 18 In this study, we identified an atr terpenoid gene cluster from S. atratus Go66. Subsequently, this gene cluster was cloned and heterologously expressed in S. albus J1074, which led to isolation of three new labdane diterpenoids featuring an unprecedented 6/6/5-fused tricyclic skeleton, designated as atralabdans A−C (1−3), and a known compound, labdanmycin A.…”

“…However, these clusters are frequently minimally expressed or inactive under standard conditions. Li observed that most diterpenes tapped through genome mining in streptomycetes exhibit novel skeletons, and the activation and exploration of the terpenoid gene clusters within streptomycetes holds the potential for discovery of novel terpenoids …”

Actinomycetes as Producers of Biologically Active Terpenoids: Current Trends and Patents

“…The strains S. sanglieri YIM 121209-2 [91], S. anulatus YIM 101882 [92], and Streptomyces sp. RM-14-6 [93] produced new 15-hydroxy-(+)-epi-cubenol (34), 5,11-epoxy-10-cadinanol (35), and isopterocarpolone (41), respectively.…”

“…Terpene biosynthesis by actinomycetes is an actual research area discussed in research and review publications. However, the specialized reviews are focused on certain genera of actinomycetes and/or groups of terpene derivatives [ 41 , 42 ], bacterial terpenome [ 43 ], and evolution and ecology of microbial terpenoids [ 44 ]. The present review aims at assessing the biosynthetic potential ( via the patent analysis in particular) of various representatives of Actinomycetes as producers of a wide range of biologically active terpenoids, including hybrid metabolites (meroterpenoids).…”