Applied Microbiology and Biotechnology

, Volume 103, Issue 19, pp 8087–8103 | Cite as

A cytochrome P450 monooxygenase gene required for biosynthesis of the trichothecene toxin harzianum A in Trichoderma

  • Rosa E. Cardoza
  • Susan P. McCormick
  • Laura Lindo
  • Hye-Seon Kim
  • Elías R. Olivera
  • David R. Nelson
  • Robert H. ProctorEmail author
  • Santiago GutiérrezEmail author
Applied genetics and molecular biotechnology


Trichothecenes are sesquiterpene toxins produced by diverse fungi, including some species of Trichoderma that are potential plant disease biocontrol agents. Trichoderma arundinaceum produces the trichothecene harzianum A (HA), which consists of the core trichothecene structure (12,13-epoxytrichothec-9-ene, EPT) with a linear polyketide-derived substituent (octa-2,4,6-trienedioyl) esterified to an oxygen at carbon atom 4. The genes required for biosynthesis of EPT and the eight-carbon polyketide precursor of the octa-2,4,6-trienedioyl substituent, as well as for esterification of the substituent to EPT have been described. However, genes required for conversion of the polyketide (octa-2,4,6-trienoic acid) to octa-2,4,6-trienedioyl-CoA, the immediate precursor of the substituent, have not been described. Here, we identified 91 cytochrome P450 monooxygenase genes in the genome sequence of T. arundinaceum, and provided evidence from gene deletion, complementation, cross-culture feeding, and chemical analyses that one of them (tri23) is required for conversion of octa-2,4,6-trienoic acid to octa-2,4,6-trienedioyl-CoA. The gene was detected in other HA-producing Trichoderma species, but not in species of other fungal genera that produce trichothecenes with an octa-2,4,6-trienoic acid-derived substituent. These findings indicate that tri23 is a trichothecene biosynthetic gene unique to Trichoderma species, which in turn suggests that modification of octa-2,4,6-trienoic acid during trichothecene biosynthesis has evolved independently in some fungi.


Trichoderma trichothecenes Harzianum A Cytochrome P450 monooxygenase Genome sequencing Transcriptomics Secondary metabolites 



We thank Crystal Probyn, José Alvarez, Jennifer Teresi, Amy McGovern, and Christine Hodges for technical assistance.

Data Availability Statement

Sequences of the genomic regions containing tri18-tri17 and tri23 when present, from Trichoderma protrudens, T. turrialbense, T. albolutescens, and Hypocrea rodmanii, have been submitted to the GenBank database of the National Center for Biotechnology Information. The accession numbers for these sequences are as follows: MN136191 Hypocrea rodmanii, MN136192 T. albolutescens, MN136193 T. protrudens, and MN136194 T. turrialbense.

Genome sequences of T. arundinaceum and T. brevicompactum are available (Proctor et al. 2018).


This work was supported by the Spanish Ministry of Science, Innovation and Universities (MICINN-RTI2018-099600-B-100 to S.G.). Funding was also provided by the USDA-ARS National Program for Food Safety (NP108). L. Lindo was granted a fellowship by the University of León (Spain).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human or animals performed by any of the authors.


Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture. USDA is an equal opportunity provider and employer.

Supplementary material

253_2019_10047_MOESM1_ESM.pdf (12.3 mb)
ESM 1 (PDF 12.3 mb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Area of MicrobiologyUniversity of LeónPonferradaSpain
  2. 2.National Center for Agricultural Utilization ResearchUnited States Department of AgriculturePeoriaUSA
  3. 3.Area of Biochemistry and Molecular BiologyUniversity of LeónLeónSpain
  4. 4.Dept. of Microbiology, Immunology and BiochemistryUniversity of TennesseeMemphisUSA

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