Cryptic and Stereospecific Hydroxylation, Oxidation, and Reduction in Platensimycin and Platencin Biosynthesis

• DOI: 10.1021/jacs.8b13452
• Publication Date: 2019-02-08T15:41:40Z
• Authors: Liao-Bin Dong; Xiao Zhang; Jeffrey D. Rudolf; Ming-Rong Deng; Edward Kalkreuter; Alexis J. Cepeda; Hans Renata; Ben Shen
• Keywords: Hydroxylation; Stereospecificity

Platensimycin (PTM) and platencin (PTN) are highly functionalized bacterial diterpenoids of ent-kauranol ent-atiserene biosynthetic origin. C7 oxidation in the B-ring plays a key role generating structural complexity known for ent-kaurane ent-atisane derived diterpenoids. While all three patterns, α-hydroxyl, β-hydroxyl, ketone, at seen both diterpenoids, their origins remain largely unknown. We previously established that PTM PTN produced by single machinery, featuring cryptic oxidations B-rings transform precursors into characteristic scaffolds. Here, we report three-enzyme cascade affording α-hydroxylation biosynthesis. Combining vitro vivo studies, show PtmO3 PtmO6 two functionally redundant α-ketoglutarate-dependent dioxygenases generate β-hydroxyl on each scaffolds, PtmO8 PtmO1, pair NAD+/NADPH-dependent dehydrogenases, subsequently work concert to invert α-hydroxyl via ketone intermediate. represent first dedicated β-hydroxylases characterized date and, together with provide an account patterns may shed light other modifications bacterial, plant, fungal diterpenoid Given unprecedented activities oxidations, PtmO3, PtmO6, PtmO8, PtmO1 enrich growing toolbox novel enzymes could be exploited as biocatalysts rapidly access complex natural products.