Fungal Highly Reducing Polyketide Synthases Biosynthesize Salicylaldehydes That Are Precursors to Epoxycyclohexenol Natural Products
Fungal Highly Reducing Polyketide Synthases Biosynthesize Salicylaldehydes That Are Precursors to Epoxycyclohexenol Natural Products
复制标题
真菌高度还原性聚酮化合物生物合成水杨醛，水杨醛是环氧环己烯醇天然产物的前体
DOI：
10.1021/jacs.9b09669
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发表时间：
2019-12-18
影响因子：
15
通讯作者：
Tang, Yi
中科院分区：
文献类型：
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作者：
Liu, Ling;Tang, Man-Cheng;Tang, Yi
真菌高度还原聚酮酶（HRPKS）是一种高度程序化的多结构域酶，可合成还原聚酮结构。最近的报道表明水杨醛是由HRPKS生物合成基因簇合成的，这是基于已知的HRPKS酶学的意料之外的。使用编码许多氧化还原酶的绿色木霉HRPKS基因簇的基因组挖掘，我们揭示了HRPKS途径在芳香族产物如水杨醛4的生物合成中所使用的策略，其可以被氧化修饰为环氧环己醇天然产物氧化物1。我们表明，选择性β-羟基基团的线性HRPKS产品分别再氧化为β-酮的短链脱氢酶/还原酶，这使得分子内羟醛缩合和芳构化。我们的工作扩展了通过HRPKS途径可获得的天然产物的化学空间。
Fungal highly reducing polyketide synthases (HRPKSs) are highly programmed multidomain enzymes that synthesize reduced polyketide structures. Recent reports indicated salicylaldehydes are synthesized by HRPKS biosynthetic gene clusters, which are unexpected based on known enzymology of HRPKSs. Using genome mining of a Trichoderma virens HRPKS gene cluster that encodes a number of redox enzymes, we uncover the strategy used by HRPKS pathways in the biosynthesis of aromatic products such as salicylaldehyde 4, which can be oxidatively modified to the epoxycyclohexanol natural product trichoxide 1. We show selective beta-hydroxyl groups in the linear HRPKS product are individually reoxidized to beta-ketones by short-chain dehydrogenase/reductase enzymes, which enabled intramolecular aldol condensation and aromatization. Our work expands the chemical space of natural products accessible through HRPKS pathways.