The backbone of HSAF is formed through a hybrid PKS-NRPS cluster containing one
nonribosomal peptide synthase (NRPS) module and one
polyketide synthase (PKS) module.[2][6][7][8] The single PKS module functions in a non-canonical fashion in that it is an iterative type I PKS responsible for the generation of the two unique
polyketides needed in the backbone of HSAF using
malonyl-CoA as both the starter and extender unit, while the NRPS module is responsible for the linking of the
polyketides to an
L-ornithine unit and the initial cyclization to create the tetramate back bone.[2][7][8] The coding region related to HSAF production contains a PKS-NRPS with a total of 9 domains, (KS-AT-DH-KR-ACP-C-A-PCP-TE), while a cascade of
FAD-dependent redox reactions (OX1-OX4) flank the PKS-NRPS cluster proposed to be responsible for formation of the 5,5,6-tricyclic system, there are additional coding regions for a putative regulator, an
arginase for L-ornithine production from
Arginine, and a transporter which flank the PKS-NRPS.[2][3][7][8]
^Li, Shaojie; Calvo, Ana M.; Yuen, Gary Y.; Du, Liangcheng; Harris, Steven D. (2009). "Induction of cell wall thickening by the antifungal compound dihydromaltophilin disrupts fungal growth and is mediated by sphingolipid biosynthesis". The Journal of Eukaryotic Microbiology. 56 (2): 182–187.
doi:
10.1111/j.1550-7408.2008.00384.x.
ISSN1550-7408.
PMID21462551.
S2CID33464609.