Fungal naphthoquinones, like red bikaverin, are of interest due to their growing applications in designing pharmaceutical products. Though considerable work has been done on the elucidation of bikaverin biosynthesis pathway in Fusarium fujikuroi, very few reports are available regarding its bioproduction in F. oxysporum. We are hereby proposing a putative metabolic pathway for bikaverin bioproduction in a wild F. oxysporum strain by cross-linking the pigment profiles we obtained under two different fermentation conditions with literature. Naphthoquinone pigments were extracted with a pressurized liquid extraction method, and characterized by HPLC–DAD and UHPLC-HRMS. The results led to the conclusions that the F. oxysporum LCP531 strain was able to produce bikaverin and its various intermediates, e.g., pre-bikaverin, oxo-pre-bikaverin, dinor-bikaverin, me-oxo-pre-bikaverin, and nor-bikaverin, in submerged cultures in various proportions. To our knowledge, this is the first report of the isolation of these five bikaverin intermediates from F. oxysporum cultures, providing us with steady clues for confirming a bikaverin metabolic pathway as well as some of its regulatory patterns in the F. oxysporum LCP531 strain, based on the previously reported model in F. fujikuroi. Interestingly, norbikaverin accumulated along with bikaverin in mycelial cells when the strain grew on simple carbon and nitrogen sources and additional cofactors. Along bikaverin production, we were able to describe the excretion of the toxin beauvericin as main extrolite exclusively in liquid medium containing complex nitrogen and carbon sources, as well as the isolation of ergosterol derivate in mycelial extracts, which have potential for pharmaceutical uses. Therefore, culture conditions were also concluded to trigger some specific biosynthetic route favoring various metabolites of interest. Such observation is of great significance for selective production of pigments and/or prevention of occurrence of others (aka mycotoxins).

中文翻译：

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野生尖孢镰刀菌LCP531菌株中生物合成比卡维林及其中间体的推定代谢途径

真菌萘醌，如红色比卡维林，由于其在设计药物产品中的日益增长的应用而备受关注。虽然大量的工作已经在bikaverin生物合成途径的阐明做镰刀恶苗病，很少有报告可关于其在生物生产F. 病菌。我们据此通过文献中在两种不同发酵条件下获得的色素图谱的交联，提出了在野生镰刀菌菌株中比卡维林生物生产的推定代谢途径。萘醌颜料采用加压液体萃取法萃取，并通过HPLC-DAD和UHPLC-HRMS进行表征。导致结论如下结果：F. 病菌LCP531菌株能够在淹没培养物中以不同比例生产出比卡维林及其各种中间体，例如前比卡维林，氧代前比卡维林，dinor-比卡维林，me-oxo-前比卡维林和nor-bikaverin。据我们所知，这是这五种隔离的第一次报告从bikaverin中间体F. 病菌文化，为我们提供了用于确认bikaverin代谢途径，以及一些在其监管模式稳定线索尖孢镰刀菌LCP531应变，基于先前报道的F.kujikuroi模型。有趣的是，当菌株在简单的碳和氮源以及其他辅助因子上生长时，诺必卡维林与比卡维林一起在菌丝体细胞中积累。在比卡韦林生产过程中，我们能够描述毒素鲍维霉素排泄在主要含有复杂氮和碳源的液体培养基中作为主要外泌体，以及在菌丝体提取物中麦角固醇衍生物的分离，这对于制药具有潜在的应用。因此，还总结了培养条件以触发一些有利于各种目的代谢物的特定生物合成途径。这样的观察对于颜料的选择性生产和/或防止其他物质（aka霉菌毒素）的发生具有重要意义。