Data from: Biotransformation of labdane and halimane diterpenoids by two filamentous fungi strains

Biotransformation of natural products by filamentous fungi is a powerful and effective approach to achieve derivatives with valuable new chemical and biological properties. Despite diterpenoid substrates exhibit good susceptibility towards fungi enzymes, there have been no studies concerning the microbiological transformation of halimane-type diterpenoids up to now. In this work, we investigated the capability of Fusarium oxysporum (a fungus isolated from the rhizosphere of Senna spectabilis) and Myrothecium verrucaria (an endophyte) to transform halimane (1) and labdane (2) acids isolated from Hymenaea stigonocarpa (Fabaceae). Feeding experiments resulted in the production of six derivatives, including hydroxy, oxo, formyl, and carboxy analogues. Incubation of 1 with F. oxysporum afforded 2-oxo-derivative (3), while bioconversion with M. verrucaria provided 18,19-dihydroxy (4), 18-formyl (5), and 18-carboxy (6) bioproducts. Transformation of substrate 2 mediated by F. oxysporum produced a 7-hydroxy (7) derivative, whilst M. verrucaria yielded 7- (7) and 3-hydroxy (8) metabolites. Unlike F. oxysporum, which showed a preference to transform ring B, M. verrucaria, exhibited the ability to hydroxylate both rings A and B from substrate 2. Additionally, compounds 1–8 were evaluated for inhibitory activity against Hr-AChE and Hu-BChE enzymes through ICER-IT-MS/MS assay.

利用丝状真菌对天然产物进行生物转化，是制备具有新颖化学结构与优良生物学活性衍生物的高效策略。尽管二萜类底物对真菌酶系展现出良好的底物适应性，但截至目前，尚未有关于halimane型二萜类化合物（halimane-type diterpenoids）的微生物转化研究报道。本研究考察了尖孢镰刀菌（Fusarium oxysporum，分离自亮叶决明Senna spectabilis根际）与疣孢漆斑菌（Myrothecium verrucaria，一株内生真菌）对分离自狭果香脂豆Hymenaea stigonocarpa（豆科Fabaceae）的halimane型二萜酸（化合物1）以及劳丹烷型二萜酸（labdane-type diterpenoid acid，化合物2）的生物转化能力。通过底物饲喂实验，共获得6种衍生物，涵盖羟基化、酮基化、甲酰化与羧基化产物类型。将化合物1与尖孢镰刀菌共孵育，得到2-酮基衍生物（3）；而与疣孢漆斑菌共孵育则得到18,19-二羟基衍生物（4）、18-甲酰基衍生物（5）与18-羧基衍生物（6）。底物2经尖孢镰刀菌介导的转化得到7-羟基衍生物（7）；而疣孢漆斑菌则将其转化为7-羟基衍生物（7）与3-羟基衍生物（8）。不同于偏好修饰底物2的B环的尖孢镰刀菌，疣孢漆斑菌可对底物2的A环与B环均实现羟基化修饰。此外，本研究通过ICER-IT-MS/MS法，对化合物1~8开展了针对家蝇乙酰胆碱酯酶（Hr-AChE）与人丁酰胆碱酯酶（Hu-BChE）的抑制活性评价。