Metabolic pathway gene clusters in filamentous fungi.

Clusters of functionally related genes are a general feature of prokaryotic gene organization but are much less prevalent in eukaryotes. The discovery that genes for certain types of metabolic pathways are clustered in filamentous fungi is relatively recent. Only 8 years ago in a discussion of the proline utilization pathway genes, Hull et al. (1989) commented that ‘‘The organization and regulation of the genes involved in L-proline catabolism in the ascomycete fungus Aspergillus nidulans are of particular interest because, rather unusually for functionally related eukaryotic genes, they are all clustered.’’ This view was supported by studies of metabolic pathway gene linkage relationships from a variety of eukaryotes. Although genetic evidence was available suggesting that some metabolic pathway genes were closely linked in A. nidulans (see Clutterbuck, 1992), recognition of gene clustering as an important feature of fungal metabolic pathways had to await the molecular characterization of specific pathways. Fungal gene clusters can be broadly defined as the close linkage of two or more genes that participate in a common metabolic or developmental pathway. Fungi possess numerous pathways for what can be described as ‘‘dispensable’’ metabolic functions, and research over the last 5 years has shown that the genes for these dispensable pathways are often organized in gene clusters. The term dispensable metabolic pathways is used here to describe pathways that either are not required for growth or are only required for growth under a limited range of conditions. Dispensable metabolic pathways are typically expressed under suboptimal growth conditions and most likely function to enhance fungal survival in response to nutrient deprivation or competing organisms. In this review, two major types of dispensable metabolic pathways will be discussed, catabolic pathways for the utilization of low-molecular-weight nutrients such as proline or quinate (nutrient utilization pathways) and biosynthetic pathways for low-molecularweight compounds which include antibiotics and mycotoxins (natural product pathways). Nutrient utilization pathways increase the metabolic versatility of filamentous fungi, enabling them to utilize a variety of complex compounds as alternative sources of nutrients. Expression of the appropriate catabolic pathways can be critically important for survival under limiting nutrient growth conditions. However, many of these nutrients are not commonly encountered by fungi, so there is little benefit derived from expressing pathway genes constitutively. To ensure that the required catabolic pathways are expressed appropriately in response to changing nutritional conditions while simultaneously limiting the loss of cellular resources due to unnecessary pathway gene expression, fungi have developed complex regulatory systems. To date, enzymatic and regulatory genes for four well-studied dispensable catabolic pathways (quinate, ethanol, proline, Fungal Genetics and Biology 21, 17–29 (1997) Article No. FG970970