McCadden Caitlin A, Alsup Tyler A, Ghiviriga Ion, Rudolf Jeffrey D
Department of Chemistry, University of Florida, Gainesville, FL, USA.
J Ind Microbiol Biotechnol. 2024 Dec 31;52. doi: 10.1093/jimb/kuaf003.
Biocatalysis provides access to synthetically challenging molecules and commercially and pharmaceutically relevant natural product analogs while adhering to principles of green chemistry. Cytochromes P450 (P450s) are among the most superlative and versatile oxidative enzymes found in nature and are desired regio- and stereoselective biocatalysts, particularly for structurally complex hydrocarbon skeletons. We used 10 genome-sequenced Streptomyces strains, selected based on their preponderance of P450s, to biotransform the bioactive diterpenoid abietic acid. We isolated and structurally characterized seven oxidized abietic acid derivatives from three different strains, including four products that are new bacterial biotransformants or enzymatic products. Oxidations (hydroxylation, dehydrogenation, and aromatization) were seen on both the B and C rings of abietic acid and five products had multiple modifications. Notable conversions observed in the study were that of abietic acid to 15-hydroxy-7-oxo-8,11,13-abietatrien-18-oic acid, 7, which involves multiple hydroxylation reactions and dehydrogenation. The findings from this study will lead to identifying P450s or other enzymes that may act as general biocatalysts to modify abietanes and other labdane-type diterpenoid skeletons.
ONE-SENTENCE SUMMARY: Genome-guided biotransformation of the bioactive diterpenoid abietic acid in Streptomyces yielded seven oxidized derivatives including four that have not been previously seen from bacteria.
生物催化在遵循绿色化学原则的同时，能够合成具有挑战性的分子以及具有商业和药学相关性的天然产物类似物。细胞色素P450（P450s）是自然界中最出色且用途广泛的氧化酶之一，是理想的区域和立体选择性生物催化剂，尤其适用于结构复杂的烃骨架。我们使用了10种基于其P450优势而挑选的基因组测序链霉菌菌株，对生物活性二萜类化合物枞酸进行生物转化。我们从三种不同的菌株中分离并对七种氧化枞酸衍生物进行了结构表征，其中包括四种新的细菌生物转化产物或酶促产物。枞酸的B环和C环均发生了氧化反应（羟基化、脱氢和芳构化），并且有五种产物具有多种修饰。该研究中观察到的显著转化是枞酸转化为15-羟基-7-氧代-8,11,13-枞三烯-18-酸（7），这涉及多个羟基化反应和脱氢反应。这项研究的结果将有助于鉴定可能作为通用生物催化剂来修饰枞烷和其他半日花烷型二萜骨架的P450或其他酶。
链霉菌中生物活性二萜类化合物枞酸的基因组导向生物转化产生了七种氧化衍生物，其中四种是细菌中以前未见的。
