AbmV Catalyzes Tandem Ether Installation and Hydroxylation during Neoabyssomicin/Abyssomicin Biosynthesis

Abstract

Members of the abyssomicin class of natural products are characterized by a novel vinylic bridged ether ring. In this study, in vivo gene inactivation, structure elucidation of the accumulated intermediate abyssomicin 6, and in vitro enzyme assays enabled the identification of a cytochrome P450 enzyme, AbmV. AbmV carries out domino reactions involving bridged ether installation and C-11 hydroxylation during the biosynthesis of neoabyssomicins/abyssomicins in S. koyangensis SCSIO 5802.

Engineering cytochrome P450 enzyme systems for biomedical and biotechnological applications

“…Notably, the protein pair SelFdx1499 (Fe 2 S 2 )/SelFdR0978 (plastidic-type FdR) from the cyanobacterial strain Synechococcus elongatus PCC 7942 has been shown to be an optimal combination for supporting in vitro reactions of prokaryotic P450s, including MycG, PikC, P450sca-2 and others (76). Besides the above-mentioned P450 reaction matrix network, the protein pair SelFdx1499/SelFdR0978 has also been shown to be optimal for the site-selective hydroxylation of CsA by CYP-sb21 and CYP-pa1 (45,47), the uncommon ester-to-ether transformation catalyzed by Rif16 in rifamycin biosynthesis (77), the tandem ether installation and hydroxylation by AmbV involved in neoabyssomicin/abyssomicin biosynthesis (78), and the biosynthesis of phenylserine (␤-OH-Phe) unit in atratumycin by Atr27 (79).…”

Synthetic and biosynthetic methods for selective cyclisations of 4,5-epoxy alcohols to tetrahydropyrans

“…117 To date, ∼30 abyssomicins have been isolated and characterised, and they display a wide range of promising bioactivities including antibacterial and antiviral activities. 118 Combining in vivo gene inactivation with in vitro biochemical studies, Li et al showed that the ether ring formation and hydroxylation in abyssomicin 2 biosynthesis is catalysed by the cytochrome P450 AbmV. 118 This was proposed to result from a domino reaction sequence involving, (i) epoxidation of the 11,12-alkene in abyssomicin 6 to generate an epoxide intermediate 210 followed by, (ii) epoxide ring-opening via nucleophilic attack of the tetronate OH upon C12 to afford abyssomicin 2 (Scheme 48).…”

“…This epoxy alcohol 214 Scheme 48 Proposed late stage pathway for abyssomicin biosynthesis. 118 Scheme 47 Proposed formation of the hydroxylated THP in ambruticin biosynthesis. 114 Scheme 49 Proposed late stages biosynthesis of citreoviridin.…”

Marine Spirotetronates: Biosynthetic Edifices That Inspire Drug Discovery

“…Conversion of abyssomicin 6 ( 13 ) to abyssomicin 2 ( 14 ) is biosynthetically accomplished by AbmV, a P450 enzyme responsible for C11-C12 tandem epoxidation and SN2-epoxide opening sequence (Figure 2b) [53]. Analogous enzymes are proposed to oxidize other abyssomicins but AbmV is the first isolated enzyme and is relevant to the newly discovered neoabyssomicins [54].…”