The Netherlands & Kluyver Centre for Genomics of Industrial Fermentation, PO Box 5057, 2600 GA Delft, The Netherlands.
Appl Microbiol Biotechnol. 2011 Aug;91(3):447-60. doi: 10.1007/s00253-011-3391-3. Epub 2011 Jun 18.
Heme biosynthesis in fungal host strains has acquired considerable interest in relation to the production of secreted heme-containing peroxidases. Class II peroxidase enzymes have been suggested as eco-friendly replacements of polluting chemical processes in industry. These peroxidases are naturally produced in small amounts by basidiomycetes. Filamentous fungi like Aspergillus sp. are considered as suitable hosts for protein production due to their high capacity of protein secretion. For the purpose of peroxidase production, heme is considered a putative limiting factor. However, heme addition is not appropriate in large-scale production processes due to its high hydrophobicity and cost price. The preferred situation in order to overcome the limiting effect of heme would be to increase intracellular heme levels. This requires a thorough insight into the biosynthetic pathway and its regulation. In this review, the heme biosynthetic pathway is discussed with regards to synthesis, regulation, and transport. Although the heme biosynthetic pathway is a highly conserved and tightly regulated pathway, the mode of regulation does not appear to be conserved among eukaryotes. However, common factors like feedback inhibition and regulation by heme, iron, and oxygen appear to be involved in regulation of the heme biosynthesis pathway in most organisms. Therefore, they are the initial targets to be investigated in Aspergillus niger.
真菌宿主菌株中的血红素生物合成在与分泌血红素过氧化物酶的生产有关的方面引起了相当大的兴趣。类 II 过氧化物酶被认为是工业中污染化学过程的环保替代品。这些过氧化物酶天然由担子菌少量产生。由于其具有较高的蛋白质分泌能力，丝状真菌如 Aspergillus sp. 被认为是适合蛋白质生产的宿主。出于过氧化物酶生产的目的，血红素被认为是一个潜在的限制因素。然而，由于其高疏水性和高成本，血红素的添加并不适合大规模生产过程。为了克服血红素的限制作用，首选情况是增加细胞内血红素水平。这需要深入了解生物合成途径及其调控。在这篇综述中，讨论了血红素生物合成途径的合成、调控和运输。尽管血红素生物合成途径是一个高度保守且严格调控的途径，但调控模式在真核生物中似乎并不保守。然而，在大多数生物体中，血红素、铁和氧的反馈抑制和调节等共同因素似乎参与了血红素生物合成途径的调节。因此，它们是最初要在黑曲霉中进行研究的目标。
