1999年,第一个生物合成基因簇(BGC),合成毒力因子DHN黑色素,以烟曲霉为特征。从那以后,在该物种中,有19个额外的BGC与特定的次级代谢产物(SM)相关。这里,我们提供了烟曲霉BGC发现的全面时间表,并发现最初的进展集中在通常表达的SM周围,其中化学结构为产生BGC的基本原理鉴定提供了依据(例如,神经胶质毒素,熏烟,Fumitremorgin,PseurotinA,螺旋醇酸,氟喹唑啉)。在ΔlaeA突变体的转录分析之后,进一步的进步,这有助于识别内生罗素,烟曲霉素,hexadehydroxyastechrome,胰蛋白酶,和FumisoquinBGC。这些SM及其前体是大多数烟曲霉研究中通常产生的代谢物。其他BGC/SM对的表征需要额外的努力,如诱导治疗,包括与细菌的共培养(富马酸/新卡霉素,Fumigermin)或铜饥饿下的生长(富米缬氨酸,Fumicicolin).最后,通过过表达技术发现了四个BGC/SM对,包括使用异源宿主(万霉素/新卡霉素,Fumihopaside,Sphingofungin,和sartorypyrone)。对两个研究最多的烟曲霉分离株的初步分析,Af293和A1160,表明两者都藏有约。34-36BGC。然而,对264个可用的烟曲霉基因组的检查显示了多达20个额外的BGC,一些菌株在BGC数量和组成上显示出相当大的差异。这些新的BGC为这一重要物种的次生代谢表征提供了新的前沿。
In 1999, the first biosynthetic gene cluster (BGC), synthesizing the virulence factor DHN melanin, was characterized in Aspergillus fumigatus. Since then, 19 additional BGCs have been linked to specific secondary metabolites (SMs) in this species. Here, we provide a comprehensive timeline of A. fumigatus BGC discovery and find that initial advances centered around the commonly expressed SMs where chemical structure informed rationale identification of the producing BGC (e.g., gliotoxin, fumigaclavine, fumitremorgin, pseurotin A, helvolic acid, fumiquinazoline). Further advances followed the transcriptional profiling of a ΔlaeA mutant, which aided in the identification of endocrocin, fumagillin, hexadehydroastechrome, trypacidin, and fumisoquin BGCs. These SMs and their precursors are the commonly produced metabolites in most A. fumigatus studies. Characterization of other BGC/SM pairs required additional efforts, such as induction treatments, including co-culture with bacteria (fumicycline/neosartoricin, fumigermin) or growth under copper starvation (fumivaline, fumicicolin). Finally, four BGC/SM pairs were discovered via overexpression technologies, including the use of heterologous hosts (fumicycline/neosartoricin, fumihopaside, sphingofungin, and sartorypyrone). Initial analysis of the two most studied A. fumigatus isolates, Af293 and A1160, suggested that both harbored ca. 34-36 BGCs. However, an examination of 264 available genomes of A. fumigatus shows up to 20 additional BGCs, with some strains showing considerable variations in BGC number and composition. These new BGCs present a new frontier in the future of secondary metabolism characterization in this important species.