Novel Cyclohexyl Meroterpenes Produced by Combinatorial Biosynthesis

Reconstitution of Polyketide-Derived Meroterpenoid Biosynthetic Pathway in Aspergillus oryzae

“…The generation of the 10S-epoxide in the Aspergillus expression system was also reported in the synthesis of the unique orthoester-bearing DMOA meroterpenoid novofumigatonin [29]. Recently, we produced novel meroterpenoids by introducing meroterpenoid cyclases from four different biosynthetic pathways into the A. oryzae host producing 10'Repoxyfarnesyl-3,5-DMOA methyl ester, and obtained two novel mono-cyclized meroterpenoids [25]. It is intriguing that the four different meroterpenoid cyclases produced the same products from the non-native substrate.…”

“…Recently, we produced novel meroterpenoids by introducing meroterpenoid cyclases from four different biosynthetic pathways into the A. oryzae host producing 10’ R -epoxyfarnesyl-3,5-DMOA methyl ester, and obtained two novel mono-cyclized meroterpenoids [ 25 ]. It is intriguing that the four different meroterpenoid cyclases produced the same products from the non-native substrate.…”

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

“…Despite its simplicity, this strategy yielded six previously unreported meroterpenoids, demonstrating the effectiveness of our methodology in discovering new natural products. Given the increasing elucidation of fungal meroterpenoid pathways in recent years, similar approaches could be applied to other meroterpenoid biosynthetic processes, as reported in a recent study that yielded new DMOA-derived meroterpenoids with a monocyclic terpenoid moiety through pathway engineering [ 23 ]. Furthermore, the meroterpenoids produced in this study could be accepted by downstream enzymes in each pathway, further expanding the structural diversity of fungal meroterpenoids and potentially aiding the functional characterization of these tailoring enzymes.…”

Engineering fungal terpene biosynthesis

“…92 In a combinatorial biosynthesis approach biosynthetic genes for the biosynthesis of 134 and for the terpene synthase AndB were heterologously expressed in A. oryzae, resulting in the new cyclisation products 140 and 141 (Scheme 24B). 93 The biosynthesis of the fungal meroterpenoid xenovulene A (148) in Acremonium strictum has been studied by Cox and coworkers through heterologous expression in A. oryzae (Scheme 25A). 94 The pathway involves formation of methylorcinaldehyde (142) by the polyketide synthase AsPKS1, followed by FAD-dependent oxidation to 143 by AsL1.…”

“…92 In a combinatorial biosynthesis approach biosynthetic genes for the biosynthesis of 134 and for the terpene synthase AndB were heterologously expressed in A. oryzae , resulting in the new cyclisation products 140 and 141 (Scheme 24B). 93…”