Chemistry Reference
In-Depth Information
POLYKETIDES IN FUNGI
THOMAS J. SIMPSON AND RUSSELL J. COX
School of Chemistry, University of Bristol, Bristol, United Kingdom
Fungi produce a wide variety of biologically active compounds. Among these com-
pounds, the polyketides form a large and structurally diverse group. These compounds
are synthesized by highly programmed, large iterative multifunctional proteins, which
are called the polyketide synthases. This review describes the structure and biosynthe-
sis of polyketide fungal metabolites and highlights recent work on the links between
gene sequence, protein architecture, and biosynthetic programming for fungal polyke-
tide synthases.
Polyketides have long been recognized as one of the most important classes of
secondary metabolites (1). They occur in plants, bacteria, and marine organisms
as well as in fungi. Fungal polyketides vary from the simplest monocyclic aro-
matic compounds, for example, orsellinic (
1
) and 6-methylsalicylic (6-MSA) (
2
)
acids to polycyclic aromatics such as citrinin (
3
), alternariol (
4
), islandicin (
5
),
deoxyherqueinone (
6
), and norsolorinic acid (
7
). Although initially associated
with the formation of aromatic compounds, many polyketides are nonaromatic
(e.g., the macrolide decarestrictine D (
8
), long-chain polyfunctional molecules
exemplified by T-toxin (
9
) and the decalins, lovastatin (
10
), and compactin (
11
)).
Many other metabolites consist of an aromatic ring attached to a more highly
reduced moiety (e.g., zeralanenone (
12
), dehydrocurvularin (
13
), and mono-
cerin (
14)
). Additional diversity results from extensive oxidative metabolism
of preformed polyketide structures (e.g., penicillic acid (
15
) and patulin (
16
)),
which are formed from cleavage and rearrangement of 6-MSA and orsellinic
acid, respectively, and indeed ring cleavage is a very common feature with
