**1. Introduction**

The symbiosis between marine sponges and microorganisms is of considerable interest, both biologically and chemically [1,2]. Sponges are benthic organisms that have been colonizing different marine ecosystems, including coral reefs, for 600 million years [3,4]. Their survival under drastically changing conditions requires a variety of adaptations, including the evolving strategy of symbiosis with beneficial microorganisms, which has been taking place since the Precambrian Age [5]. The mutualism between marine sponges and microbial symbionts is mainly related to nutrition and defense [1,6], under the control of dedicated enzymes and active secondary metabolites [2]. Although sponges are the main source of bioactive molecules isolated from marine organisms, a certain amount of evidence indicates that they are biosynthesized by microbial symbionts [7,8]. This has also been corroborated by the massive presence of microorganisms in the mesophyl matrix of the sponges, representing around 50% of their biomass [9–11].

Fungi in the marine environment, and especially those associated with marine invertebrates, have been extensively investigated and reviewed [12,13]. A 2019 collaborative review highlighted the present state of knowledge and raised a multitude of open questions regarding the diversity and function of fungi in marine ecosystems [13].

The symbiont assemblages inside the sponge are well organized in biofilms or dense colonies and are stabilized in the skeleton network over time [14,15]. This certainly impacts their development steps and the expression of biosynthetic clusters of secondary metabolites because it is now well documented that, in fungi, secondary metabolism and life cycle among fungi are co-regulated at the genomic level [16–18].

This idea drives us to compare the metabolic profile of fungi cultivated on a gar slants and in liquid state. The result is that solid-state cultivation often leads to larger molecular diversity than classical liquid state fermentation LSF [19–21]. The major obstacle that stands against agar cultivation is the scale-up. In order to overcome such a challenge, we have developed specific innovative technologies, namely Platotex [22,23] and, more recently, Unifertex [24]. As we systematically coupled the culture of microorganisms with in-situ solid phase extraction (SPE), we also developed a specific SPE procedure for agar cultivation, termed solid-solid extraction (SSE) [25].

In the present study, we report the impact of agar-supported cultivation on the production of secondary metabolites by the marine fungi *Chrysosporium lobatum* TM-237-S5, isolated from the Red Sea sponge *Acanthella cavernosa*. *Chrysosporium lobatum* was previously reported in the literature as a mosquito pathogenic fungus [26]. However, a very limited number of secondary metabolites have been reported in the literature for the genus *Chrysosporium*. Thus, the strain *Chrysosporium queenslandicum* IFM produced naphthaquinone-type altersolanols A, B, and C, the antifungal queenslandon, a representative of the zearalenone family of mycotoxin, and the antibacterial dihydronaphthaquinones chrysoqueen and chrysolandol [27]. The diterpenoid derivative RPR113228, a farnesyl transferase inhibitor, was also attributed to *Chrysosporium lobatum*, yet the identification of the strain was only based on morphological analysis [28]. Furthermore, curvularin and dehydroculvilarin were isolated from *Chrysosporium lobatum* BK-3 [29].
