Nodulisporic Acids D−F:  Structure, Biological Activities, and Biogenetic Relationships

Abstract

Nodulisporic acids D, E, and F are the newest members of a family of nontremorogenic indole-diterpenoids that are potent, orally bioavailable, antiflea agents derived from a fungus belonging to the genus Nodulisporium. The four members of the D series are each devoid of an isoprene residue that is present at C-26 in the three nodulisporic acids described originally (the A series). Nodulisporic acid E (11a) has a simpler structure, which lacks not only the isoprene residue at C-26 but also two that form the A/B rings. Nodulisporic acid F is the simplest of all nodulisporic acids and is devoid of all three isoprene residues of the indole unit; as such, it represents the earliest biosynthetic intermediate in this series. A biogenetic grid based on mutation studies is proposed that encompasses all the known nodulisporic acids. Structure-activity relationships of the known natural nodulisporic acids have been elucidated. Within a series the most active compound possesses a dienoic acid chain, and overall, the end product of the biogenetic grid, i.e., nodulisporic acid A, exhibits the most potent antiflea activity. Additionally, the stereochemistries of C-3' ' and C-4' ' of nodulisporic acid D(2) and therefore of nodulisporic acids A(2), B(2), and C(2) have been assigned.

Indole Diterpenoids and Isocoumarin from the Fungus, Aspergillus flavus, Isolated from the Prawn, Penaeus vannamei

“…[30] and Nodulisporium sp . [31], respectively. This situation is common in the microbial community, that different microbes could produce the same type of natural products.…”

Functional analysis of a prenyltransferase gene (paxD) in the paxilline biosynthetic gene cluster

“…Prenylated indole compounds, most of which are produced by filamentous fungi, are examples of this type . These compounds are derived from polyprenyl diphosphates and tryptophan or its derivatives and show diverse chemical structures and biological activities (Dalziel et al 2005;Gonzalez et al 2003;Singh et al 2004). Among prenylated indole compounds, indole-diterpenes are unique from the following viewpoints: geranylgeranyl diphosphate (GGDP) is used as a prenyl donor in contrast to other prenylated indoles, for which dimethylallyl diphosphate (DMAPP) is the usual donor, and indole/indole-3-glycerol phosphate is used as the prenyl acceptor instead of tryptophan and its derivatives (Byrne et al 2002;Saikia et al 2008;Uchida et al 2006;Tagami et al 2013).…”

A Novel Indole-diterpenoid, JBIR-03 with Anti-MRSA Activity from Dichotomomyces cejpii var. cejpii NBRC 103559

“…Although lots of indolediterpenes such as emindole SB [5], paspaline [6], petromindole [7] and paxilline [8] were reported, the terminal ring system of these compounds commonly consisted of a 6-membered ring such as pyran. In contrast, the structure of 1 possessing the terminal ring system that consists of a 5-membered ring such as furan in this series of nodulisporic acids [9] is very rare.…”