Sonnabend Robin, Seiler Lucas, Gressler Markus
Pharmaceutical Microbiology, Friedrich-Schiller-University Jena, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Winzerlaer Strasse 2, 07745 Jena, Germany.
J Fungi (Basel). 2022 Feb 18;8(2):196. doi: 10.3390/jof8020196.
The oleaginous fungus is a safe source of polyunsaturated fatty acids (PUFA) in industrial food and feed production. Besides PUFA production, pharmaceutically relevant surface-active and antimicrobial oligopeptides were isolated from this basal fungus. Both production of fatty acids and oligopeptides rely on the biosynthesis and high turnover of branched-chain-amino acids (BCAA), especially l-leucine. However, the regulation of BCAA biosynthesis in basal fungi is largely unknown. Here, we report on the regulation of the leucine, isoleucine, and valine metabolism in . In contrast to higher fungi, the biosynthetic genes for BCAA are hardly transcriptionally regulated, as shown by qRT-PCR analysis, which suggests a constant production of BCAAs. However, the enzymes of the leucine metabolism are tightly metabolically regulated. Three enzymes of the leucine metabolism were heterologously produced in , one of which is inhibited by allosteric feedback loops: The key regulator is the α-isopropylmalate synthase LeuA1, which is strongly disabled by l-leucine, α-ketoisocaproate, and propionyl-CoA, the precursor of the odd-chain fatty acid catabolism. Its gene is not related to homologs from higher fungi, but it has been inherited from a phototrophic ancestor by horizontal gene transfer.
在工业食品和饲料生产中，产油真菌是多不饱和脂肪酸（PUFA）的安全来源。除了生产PUFA外，还从这种基础真菌中分离出了与药物相关的表面活性和抗菌寡肽。脂肪酸和寡肽的生产都依赖于支链氨基酸（BCAA）的生物合成和高周转率，尤其是L-亮氨酸。然而，基础真菌中BCAA生物合成的调控在很大程度上尚不清楚。在此，我们报道了[具体真菌名称未给出]中亮氨酸、异亮氨酸和缬氨酸代谢的调控。与高等真菌不同，如qRT-PCR分析所示，BCAA的生物合成基因几乎没有转录调控，这表明BCAAs的产量恒定。然而，亮氨酸代谢的酶受到严格的代谢调控。亮氨酸代谢的三种酶在[具体宿主未给出]中进行了异源表达，其中一种酶受到变构反馈环的抑制：关键调节因子是α-异丙基苹果酸合酶LeuA1，它受到L-亮氨酸、α-酮异己酸和丙酰辅酶A（奇数链脂肪酸分解代谢的前体）的强烈抑制。其基因与高等真菌的同源物无关，但它是通过水平基因转移从光合祖先遗传而来的。
