Fonsecaea monophora, which is very similar to Fonsecaea pedrosoi in morphological features, has been commonly misdiagnosed as F. pedrosoi. Like F. pedrosoi, F. monophora has been also identified as a predominant pathogen of Chromoblastomycosis (CBM). Melanin has been recognized as a virulence factor in several fungi, however, it is still largely unknown about the biological role of melanin and how melanin is synthesized in F. monophora. In this study, we identified two putative polyketide synthase genes (pks), AYO21_03016 (pksA) and AYO21_10638, by searching against the genome of F. monophora. AYO21_03016 and AYO21_10638 were further targeted disrupted by Agrobacterium tumefaciens-mediated transformation (ATMT). We discovered that pksA gene was the major polyketide synthase required for melanin synthesis in F. monophora, rather than AYO21_10638. Phenotypic analysis showed that, knocking out of the pksA gene attenuated melanogenesis, growth rate, sporulation ability and virulence of F. monophora, as compared with wild-type and complementation strain (pksA-C). Furthermore, the ΔpksA mutant was confirmed to be more sensitive to the oxidative stress, extreme pH environment, and antifungal drugs including itraconazole (ITC), terbinafine (TER), and amphotericin B (AMB). Taken together, these findings enabled us to comprehend the role of pksA in regulating DHN-melanin pathway and its effect on the biological function of F. monophora.

Fonsecaea monophora在形态特征上与Fonsecaea pedrosoi非常相似，常被误诊为F. pedrosoi。与F.pedrosoi一样，F. monophora也已被确定为色芽生菌病 (CBM) 的主要病原体。黑色素已被公认为是几种真菌的毒力因子，然而，黑色素的生物学作用以及黑色素如何在F. monophora 中合成仍然未知。在这项研究中，我们确定了两个假定的聚酮合成酶基因（PKS），AYO21_03016（PKSA）和AYO21_10638，通过对基因组搜索F. monophora。AYO21_03016和AYO21_10638被根癌农杆菌介导的转化 (ATMT)进一步靶向破坏。我们发现pksA基因是F. monophora黑色素合成所需的主要聚酮化合物合成酶，而不是AYO21_10638。表型分析表明，与野生型和互补菌株（pksA-C）相比，敲除pksA基因减弱了F. monophora 的黑色素生成、生长速率、孢子形成能力和毒力。此外，ΔpksA突变体被证实对氧化应激、极端 pH 环境和抗真菌药物更敏感，包括伊曲康唑 (ITC)、特比萘芬 (TER) 和两性霉素 B (AMB)。总之，这些发现使我们能够理解pksA在调节DHN-黑色素途径中的作用及其对F. monophora生物学功能的影响。